Cancers

19 pages, 7811 KB

Open AccessArticle

Fatty Acid Synthase as a Potential Metabolic Vulnerability in Ocular Adnexal Sebaceous Carcinoma

by Autumn Berlied, Isabella Boyack, Andre Vieira, Maria Gonzalez-Perez, Vikas Kumar and Cornelia Peterson

Cancers 2026, 18(2), 349; https://doi.org/10.3390/cancers18020349 - 22 Jan 2026

Viewed by 411

Abstract

Background: MYC dysregulation is frequent in ocular adnexal sebaceous carcinoma (SebCA), an aggressive malignancy without precision therapy. Fatty acid synthase (FASN) expression and lipid metabolism are commonly perturbed in high-MYC-expressing tumors; however, the role of MYC and FASN in the coregulation of [...] Read more.

Background: MYC dysregulation is frequent in ocular adnexal sebaceous carcinoma (SebCA), an aggressive malignancy without precision therapy. Fatty acid synthase (FASN) expression and lipid metabolism are commonly perturbed in high-MYC-expressing tumors; however, the role of MYC and FASN in the coregulation of lipid biosynthesis and tumorigenesis in SebCA is unknown. Methods: The aim of this study was to characterize the effects of FASN inhibition on MYC expression, oncogenic processes, and lipid profiles in vitro, using non-neoplastic human Meibomian gland epithelial cells (HMGECs) and three primary SebCA cell lines, and in vivo, utilizing a conditionally MYC-overexpressing mouse model. Results: FASN inhibition reduced cell viability, proliferation, and clonogenicity and altered the saturation profile of fatty acids across multiple lipid classes. The relative saturation of ceramides was the most variable between treatment conditions. MYC overexpression in the murine Meibomian gland promoted proliferation while suppressing sebaceous differentiation. Subsequent topical FASN inhibition further reduced sebaceous differentiation, attenuated PLIN2 expression, and induced apoptotic cell death. Conclusions: Collectively, these findings suggest that MYC expression in SebCA is responsive to FASN inhibition. Pharmacologic targeting of FASN reveals a metabolic vulnerability that may serve as a target for future therapeutic development. Full article

(This article belongs to the Special Issue Novel Treatments for Ocular and Periocular Cancers)

► Show Figures

Graphical abstract

12 pages, 262 KB

Open AccessReview

Achieving Pregnancy After Early Hormone Receptor-Positive Breast Cancer: Recent Evidence and Clinical Considerations

by Karine E. Ronan and Janice M. Walshe

Cancers 2026, 18(2), 348; https://doi.org/10.3390/cancers18020348 - 22 Jan 2026

Viewed by 351

Abstract

An increasing number of young women with hormone receptor-positive (HR+) early breast cancer desire pregnancy after treatment. Prolonged adjuvant endocrine therapy, concerns regarding recurrence risk, and treatment-related fertility decline have historically complicated reproductive decision-making in this population. This narrative review synthesizes current evidence [...] Read more.

An increasing number of young women with hormone receptor-positive (HR+) early breast cancer desire pregnancy after treatment. Prolonged adjuvant endocrine therapy, concerns regarding recurrence risk, and treatment-related fertility decline have historically complicated reproductive decision-making in this population. This narrative review synthesizes current evidence on pregnancy after early HR+ breast cancer, with particular emphasis on prospective data from the POSITIVE trial. We examine the safety of temporary endocrine therapy interruption, the impact of assisted reproductive technologies (ART) in achieving pregnancy, breastfeeding feasibility and impact, hormonal predictors of fertility, pregnancy outcomes and considerations for special populations, including BRCA mutation carriers. Retrospective studies have suggested no adverse survival impact associated with pregnancy after breast cancer. The POSITIVE trial provides prospective evidence that temporary interruption of endocrine therapy to attempt pregnancy does not increase short-term recurrence risk in selected patients. Approximately three-quarters of participants achieved pregnancy. Fertility preservation and ART were commonly used and were not associated with worse short-term oncologic outcomes. Biomarkers such as anti-Müllerian hormone offer supportive but imperfect prediction of fertility potential. Breastfeeding was feasible for many women and did not adversely affect breast cancer outcomes. Available data among BRCA mutation carriers are reassuring but largely observational. Current evidence supports the safety and feasibility of pregnancy after early HR+ breast cancer in carefully selected patients. However, longer follow-up, inclusion of higher-risk populations, and evaluation of newer therapies are needed. Individualized, multidisciplinary counselling remains central to informed decision-making. Full article

(This article belongs to the Section Cancer Causes, Screening and Diagnosis)

14 pages, 549 KB

Open AccessArticle

Combination of Metronomic Chemotherapy and Rituximab in Frail and Elderly Patients with Relapsed/Refractory Follicular Lymphoma and Ineligible for Lenalidomide Treatment: A Retrospective Analysis

by Sabrina Pelliccia, Marta Banchi, Lucrezia De Marchi, Emanuele Cencini, Claudia Seimonte, Alberto Fabbri, Andrea Nunzi, Susanna Destefano, Guido Bocci and Maria Christina Cox

Cancers 2026, 18(2), 347; https://doi.org/10.3390/cancers18020347 - 22 Jan 2026

Viewed by 301

Abstract

Background/Objectives: Relapsed or refractory follicular lymphoma (rrFL) remains difficult to treat in elderly or frail patients who cannot tolerate standard-dose immuno-chemotherapy as well as novel therapies. Metronomic chemotherapy (mCHEMO) may offer sustained antitumor activity with reduced toxicity. This study assessed the clinical activity [...] Read more.

Background/Objectives: Relapsed or refractory follicular lymphoma (rrFL) remains difficult to treat in elderly or frail patients who cannot tolerate standard-dose immuno-chemotherapy as well as novel therapies. Metronomic chemotherapy (mCHEMO) may offer sustained antitumor activity with reduced toxicity. This study assessed the clinical activity and safety of R-DEVEC or R-DEVEC-light in rrFL patients following lenalidomide discontinuation or ineligibility. Methods: Data from the ReLLi Lymphoma Registry (2013–2025) were retrospectively analyzed. Eligible patients had rrFL after ≥1 prior therapy and initiated mCHEMO at least six months before data cutoff. Thirteen patients received DEVEC or the etoposide-free DEVEC-light regimen; all but one also received rituximab. Responders received maintenance vinorelbine, low-dose prednisone, and rituximab, followed by vinorelbine-only maintenance until progression or intolerance. Responses were assessed by CT after cycle two and PET/CT at completion of six induction cycles. Results: median age was 77 years (range 58–92); most patients were frail and had advanced disease. At the end of induction, 84% achieved remission (46% CR, 38% PR), with three PR converting to CR during maintenance. After a median follow-up of 27 months, the PFS was 42% (95CI 15–69%) and the OS 73% (95CI 47–100%). A transformation occurred in one patient; the main toxicity was grade 3 neutropenia (31%). DEVEC-light showed improved tolerability versus full DEVEC, with manageable infections and rare discontinuations. Conclusions: Metronomic R-DEVEC-light is a feasible and effective disease-controlling strategy for frail, heavily pretreated rrFL patients who do not tolerate lenalidomide and are excluded from modern therapies. This schedule warrants further prospective evaluation and exploration in combination with targeted agents. Full article

(This article belongs to the Section Clinical Research of Cancer)

► Show Figures

Figure 1

14 pages, 1167 KB

Open AccessArticle

Nationwide Survival Impact of Bevacizumab Under National Reimbursement for Advanced Cervical Cancer in South Korea

by Junhwan Kim, Jieun Jang, Krishnansu S. Tewari, Kyung Su Kim, Hyun-Cheol Kang and Sokbom Kang

Cancers 2026, 18(2), 346; https://doi.org/10.3390/cancers18020346 - 22 Jan 2026

Viewed by 236

Abstract

Background: The aim of this study was to evaluate the effectiveness of bevacizumab in advanced cervical cancer (CC) patients using nationwide data after its inclusion in South Korea’s National Health Insurance (NHI), considering various clinicopathologic factors. Methods: This retrospective study analyzed 3869 advanced [...] Read more.

Background: The aim of this study was to evaluate the effectiveness of bevacizumab in advanced cervical cancer (CC) patients using nationwide data after its inclusion in South Korea’s National Health Insurance (NHI), considering various clinicopathologic factors. Methods: This retrospective study analyzed 3869 advanced CC patients from South Korea’s cancer registry (2012–2019), alongside claims and death records (2012–2021). Among these 2792 patients diagnosed after bevacizumab’s NHI inclusion (August 2015), survival outcomes were compared between those receiving bevacizumab with platinum-based chemotherapy (n = 1787, 64.0%) versus chemotherapy alone (n = 1005, 36.0%). Overall survival (OS) was assessed using Cox proportional hazard regression with inverse probability of treatment weighting. Results: Following NHI coverage of bevacizumab, median OS increased from 1.5 to 2.5 years, and the 5-year OS rate increased from 25.6% to 41.4% (weighted hazard ratio [wHR], 0.63; 95% confidence interval [CI], 0.60–0.67). Among patients receiving bevacizumab, median OS was 2.6 years compared to 2.2 years for those not receiving bevacizumab, with 5-year OS rates of 42.0% and 40.2%, respectively (wHR, 0.84; 95% CI, 0.78–0.90). Subgroup analyses revealed that bevacizumab was associated with significantly better OS in patients with prior concurrent chemoradiation therapy (CCRT) history (wHR, 0.67; 95% CI, 0.61–0.75), regardless of histologic subtype (squamous cell carcinoma [SCC]: wHR, 0.69 [95% CI, 0.61–0.78] vs. non-SCC: wHR, 0.66 [95% CI, 0.55–0.79]). Conclusions: The national investment in the implementation of bevacizumab was associated with favorable survival outcomes in advanced CC patients. Particularly, bevacizumab showed pronounced survival benefit for patients with prior CCRT history, regardless of histologic subtype. Full article

(This article belongs to the Section Clinical Research of Cancer)

► Show Figures

Figure 1

20 pages, 5169 KB

Open AccessArticle

Clinical Behavior of Aggressive Variants of Papillary Thyroid Carcinoma: A Retrospective Case–Control Study

by Jovan Ilic, Nikola Slijepcevic, Katarina Tausanovic, Bozidar Odalovic, Goran Zoric, Marija Milinkovic, Branislav Rovcanin, Milan Jovanovic, Matija Buzejic, Duska Vucen, Boban Stepanovic, Sara Ivanis, Milan Parezanovic, Milan Marinkovic and Vladan Zivaljevic

Cancers 2026, 18(2), 345; https://doi.org/10.3390/cancers18020345 - 22 Jan 2026

Viewed by 223

Abstract

Background/Objectives: Papillary thyroid carcinoma (PTC) is the most common endocrine malignancy. The classic variant (cPTC) is characterized by indolent behavior and excellent prognosis. However, rare subtypes of PTC most often exhibit adverse clinical behavior. The aim of the study was to assess the [...] Read more.

Background/Objectives: Papillary thyroid carcinoma (PTC) is the most common endocrine malignancy. The classic variant (cPTC) is characterized by indolent behavior and excellent prognosis. However, rare subtypes of PTC most often exhibit adverse clinical behavior. The aim of the study was to assess the aggressiveness of rare variants of PTC by analyzing clinicopathological characteristics (CPCs) and survival outcomes. Methods: We analyzed 80 patients with rare PTC variants treated between 2009 and 2019 who were compared with cPTC and matched with a control group for age and tumor size. The variants were categorized into high-risk (HRV: tall cell, diffuse sclerosing, columnar cell, and hobnail variants), intermediate-risk (IRV: solid variant (SV)), and low-risk (LRV: oncocytic (OV) and Warthin-like (WLV)) variants. Different CPCs (capsule and blood vessel invasion, lymphonodal metastases, microscopic and macroscopic extrathyroid extension, multifocal and bilateral presentation) and survival outcomes—overall (OS), disease-specific (DSS), and disease-free survival (DFS) were compared. Results: HRVs exhibited significantly more aggressive CPCs and worse OS, DSS, and DFS compared to cPTC (p < 0.001). IRVs showed no significant difference in CPCs or survival outcomes compared to cPTC. LRVs showed excellent survival but were associated with several unfavorable CPCs. Multivariate analysis identified classification in HRVs as the only independent predictor of recurrence (p = 0.014). Conclusions: Tumors in the HRV group should retain their status as aggressive PTC variants due to unfavorable behavior and poorer prognosis. SVs, despite earlier assumptions, do not exhibit aggressive characteristics. Although the OV and WLV have similar survival to cPTC, their potential for adverse CPCs requires caution. Full article

(This article belongs to the Special Issue Thyroid Cancer Recurrence: Integrating Surgical, Clinical, and Translational Research)

► Show Figures

Figure 1

15 pages, 1447 KB

Open AccessArticle

Prognostic Factors in the Treatment of Advanced Endometrial Cancer Patients: 12-Year Experience of an ESGO Certified Center

by Dimitrios Zouzoulas, Iliana Sofianou, Efthalia Markopoulou, Tilemachos Karalis, Kimon Chatzistamatiou, Vasilis Theodoulidis, Maria Topalidou, Eleni Timotheadou, Grigoris Grimbizis and Dimitrios Tsolakidis

Cancers 2026, 18(2), 343; https://doi.org/10.3390/cancers18020343 - 22 Jan 2026

Viewed by 224

Abstract

(1) Background: Advance-stage endometrial cancer is a rare disease that encompasses a heterogeneous group of patients. Primary surgery is the treatment of choice, while neoadjuvant chemotherapy (NACT) seems to be an alternative option for inoperable frail patients. The aim of this study was [...] Read more.

(1) Background: Advance-stage endometrial cancer is a rare disease that encompasses a heterogeneous group of patients. Primary surgery is the treatment of choice, while neoadjuvant chemotherapy (NACT) seems to be an alternative option for inoperable frail patients. The aim of this study was to identify possible prognostic factors for advance-stage endometrial cancer patients. (2) Methods: We retrospectively analyzed the records of patients with endometrial cancer that underwent surgery in the 1st Department of Obstetrics–Gynecology from 2012 to 2023. Patients with advance-stage disease (FIGO stage III–IV) were included, while those with incidental microscopic lymph node metastases after staging lymphadenectomy were excluded. (3) Results: The population of this study consisted of 89 women. Patients were obese, with moderate comorbidities and a median age of 64 years old. The majority of them (75.3%) had FIGO stage IIIC disease, while one-fourth (24.7%) presented with peritoneal metastases (FIGO stage IV). Most patients had endometrioid, high-grade tumors, with substantial lymphovascular space invasion (LVSI) and deep myometrial invasion. Complete gross resection was achieved in 92.1% of the patients. NACT was administrated in 14.6% of the population. Deep myometrial invasion and non-endometrioid histology were recognized as independent prognostic factors for worse PFS, but no association was found for OS. Concerning survival rates, the median progression-free (PFS) and overall (OS) survival were 44 and 70 months, respectively. (4) Conclusions: Myometrial invasion and histological subtypes seem to affect the recurrence rate of advanced endometrial cancer patients. NACT could likely be an alternative for primarily inoperable and frail patients, but does not appear to alter survival rates. Full article

(This article belongs to the Special Issue Advancements in Surgical Approaches for Gynecological Cancers)

► Show Figures

Figure 1

18 pages, 596 KB

Open AccessReview

Fitness in CLL

by Claudia Baratè, Ilaria Scortechini, Sara Ciofini, Paola Picardi, Ilaria Angeletti, Federica Loscocco, Alessandro Sanna, Alessandro Isidori, Elisa Grazioli and Paolo Sportoletti

Cancers 2026, 18(2), 342; https://doi.org/10.3390/cancers18020342 - 21 Jan 2026

Viewed by 397

Abstract

The increased complexity of CLL management, driven by the advent of targeted therapies, makes it necessary to redefine the concept of fitness, which until a few years ago was limited to the patient’s ability to undergo chemoimmunotherapy. In the current therapeutic landscape, fitness [...] Read more.

The increased complexity of CLL management, driven by the advent of targeted therapies, makes it necessary to redefine the concept of fitness, which until a few years ago was limited to the patient’s ability to undergo chemoimmunotherapy. In the current therapeutic landscape, fitness assessment must also consider biological age, comorbidities, and frailty, which have become increasingly relevant due to evolving treatment options and a more nuanced understanding of the elderly CLL population. In this context, the general condition of the patient should be preserved with greater attention to physical activity and nutrition. This narrative review analyzed in depth all these aspects with the aim of providing insights into fitness assessments and their actualization. Full article

(This article belongs to the Special Issue Advances in Chronic Lymphocytic Leukaemia (CLL) Research)

► Show Figures

Figure 1

16 pages, 3326 KB

Open AccessArticle

CT Body Composition Changes Predict Survival in Immunotherapy-Treated Cancer Patients: A Retrospective Cohort Study

by Shlomit Tamir, Hilla Vardi Behar, Ronen Tal, Ruthy Tal Jasper, Mor Armoni, Hadar Pratt Aloni, Rotem Iris Orad, Hillary Voet, Eli Atar, Ahuva Grubstein, Salomon M. Stemmer and Gal Markel

Cancers 2026, 18(2), 341; https://doi.org/10.3390/cancers18020341 - 21 Jan 2026

Viewed by 324

Abstract

Background: Computed tomography (CT)-derived body composition parameters, including skeletal muscle and fat indices, are prognosticators in oncology. Most studies focus on baseline body-composition parameters; however, changes during treatment may provide better prognostic value. Standardized methods for measuring/reporting these parameters remain limited. Methods: This [...] Read more.

Background: Computed tomography (CT)-derived body composition parameters, including skeletal muscle and fat indices, are prognosticators in oncology. Most studies focus on baseline body-composition parameters; however, changes during treatment may provide better prognostic value. Standardized methods for measuring/reporting these parameters remain limited. Methods: This retrospective study included patients who were treated with immunotherapy for non-small cell lung cancer (NSCLC), renal cell carcinoma (RCC), or melanoma between 2017 and 2024 and had technically adequate baseline and follow-up CT scans. Body composition was analyzed using a novel, fully automated software (CompoCT) for L3 slice selection and segmentation. Body composition indices (e.g., skeletal muscle index [SMI]) were calculated by dividing the cross-sectional area by the patient’s height squared. Results: The cohort included 376 patients (mean [SD] age 66.4 [11.4] years, 67.3% male, 72.6% NSCLC, 14.6% RCC, and 12.8% melanoma). During a median follow-up of 21 months, 220 (58.5%) died. Baseline body composition parameters were not associated with mortality, except for a weak protective effect of higher SMI (HR = 0.98, p = 0.043). In contrast, longitudinal decreases were strongly associated with increased mortality. Relative decreases in SMI (HR, 1.17; 95% CI, 1.07–1.27) or subcutaneous fat index (SFI) (HR, 1.11; 95% CI, 1.07–1.15) significantly increased mortality risk. Multivariate models showed similar concordance (0.65) and identified older age, NSCLC tumor type, and relative decreases in SMI and SFI (per 5% units) as independent predictors of mortality. Conclusions: Longitudinal decreases in skeletal muscle and subcutaneous fat were independent predictors of mortality in immunotherapy-treated patients. Automated CT-based body composition analysis may support treatment decisions during immunotherapy. Full article

(This article belongs to the Special Issue The Emerging Role of Multiplexed Imaging for Cancer Diagnosis and Therapy (2nd Edition))

► Show Figures

Figure 1

31 pages, 1934 KB

Open AccessReview

Prospective of Colorectal Cancer Screening, Diagnosis, and Treatment Management Using Bowel Sounds Leveraging Artificial Intelligence

by Divyanshi Sood, Surbhi Dadwal, Samiksha Jain, Iqra Jabeen Mazhar, Bipasha Goyal, Chris Garapati, Sagar Patel, Zenab Muhammad Riaz, Noor Buzaboon, Ayushi Mendiratta, Avneet Kaur, Anmol Mohan, Gayathri Yerrapragada, Poonguzhali Elangovan, Mohammed Naveed Shariff, Thangeswaran Natarajan, Jayarajasekaran Janarthanan, Shreshta Agarwal, Sancia Mary Jerold Wilson, Atishya Ghosh, Shiva Sankari Karuppiah, Joshika Agarwal, Keerthy Gopalakrishnan, Swetha Rapolu, Venkata S. Akshintala and Shivaram P. Arunachalam Show full author list Hide full author list

Cancers 2026, 18(2), 340; https://doi.org/10.3390/cancers18020340 - 21 Jan 2026

Viewed by 555

Abstract

Background: Colorectal cancer (CRC) is the second leading cause of cancer-related mortality worldwide, accounting for approximately 10% of all cancer cases. Despite the proven effectiveness of conventional screening modalities such as colonoscopy and fecal immunochemical testing (FIT), their invasive nature, high cost, and [...] Read more.

Background: Colorectal cancer (CRC) is the second leading cause of cancer-related mortality worldwide, accounting for approximately 10% of all cancer cases. Despite the proven effectiveness of conventional screening modalities such as colonoscopy and fecal immunochemical testing (FIT), their invasive nature, high cost, and limited patient compliance hinder widespread adoption. Recent advancements in artificial intelligence (AI) and bowel sound-based signal processing have enabled non-invasive approaches for gastrointestinal diagnostics. Among these, bowel sound analysis—historically considered subjective—has reemerged as a promising biomarker using digital auscultation and machine learning. Objective: This review explores the potential of AI-powered bowel sound analytics for early detection, screening, and characterization of colorectal cancer. It aims to assess current methodologies, summarize reported performance metrics, and highlight translational opportunities and challenges in clinical implementation. Methods: A narrative review was conducted across PubMed, Scopus, Embase, and Cochrane databases using the terms colorectal cancer, bowel sounds, phonoenterography, artificial intelligence, and non-invasive diagnosis. Eligible studies involving human bowel sound-based recordings, AI-based sound analysis, or machine learning applications in gastrointestinal pathology were reviewed for study design, signal acquisition methods, AI model architecture, and diagnostic accuracy. Results: Across studies using convolutional neural networks (CNNs), gradient boosting, and transformer-based models, reported diagnostic accuracies ranged from 88% to 96%. Area under the curve (AUC) values were ≥0.83, with F1 scores between 0.71 and 0.85 for bowel sound classification. In CRC-specific frameworks such as BowelRCNN, AI models successfully differentiate abnormal bowel sound intervals and spectral patterns associated with tumor-related motility disturbances and partial obstruction. Distinct bowel sound-based signatures—such as prolonged sound-to-sound intervals and high-pitched “tinkling” proximal to lesions—demonstrate the physiological basis for CRC detection through bowel sound-based biomarkers. Conclusions: AI-driven bowel sound analysis represents an emerging, exploratory research direction rather than a validated colorectal cancer screening modality. While early studies demonstrate physiological plausibility and technical feasibility, no large-scale, CRC-specific validation studies currently establish sensitivity, specificity, PPV, or NPV for cancer detection. Accordingly, bowel sound analytics should be viewed as hypothesis-generating and potentially complementary to established screening tools, rather than a near-term alternative to validated modalities such as FIT, multitarget stool DNA testing, or colonoscopy. Full article

(This article belongs to the Section Methods and Technologies Development)

► Show Figures

Figure 1

10 pages, 688 KB

Open AccessCommentary

QSOX1: A Mysterious Golgi-Localized Disulfide Bond Catalyst and an Emerging Cancer Regulator

by Shike Wang, Guan-Yu Xiao and Xiaochao Tan

Cancers 2026, 18(2), 339; https://doi.org/10.3390/cancers18020339 - 21 Jan 2026

Viewed by 397

Abstract

Quiescin sulfhydryl oxidase 1 (QSOX1) is a disulfide bond-forming enzyme with both disulfide isomerase and oxidoreductase activities. It plays an important role in protein folding, stability, and secretion. Growing evidence demonstrates that QSOX1 is upregulated in multiple cancer types and influences key behaviors [...] Read more.

Quiescin sulfhydryl oxidase 1 (QSOX1) is a disulfide bond-forming enzyme with both disulfide isomerase and oxidoreductase activities. It plays an important role in protein folding, stability, and secretion. Growing evidence demonstrates that QSOX1 is upregulated in multiple cancer types and influences key behaviors of cancer cells, including proliferation, migration, invasion, and metastasis. Elevated QSOX1 expression is also associated with tumor malignancy and disease relapse. However, the molecular mechanisms by which QSOX1 drives cancer progression remain incompletely understood. In this review, we summarize current knowledge of QSOX1 expression and regulation in cancer, discuss its functional roles, and highlight key unanswered questions to warrant further investigation. Full article

(This article belongs to the Special Issue The Cellular Ecosystem of Cancer: New Insights into Cell Biology)

► Show Figures

Figure 1

14 pages, 590 KB

Open AccessArticle

Behaviour Change for Physical Activity Is Feasible and Effective in Women Living with Metastatic Breast Cancer: A Pilot Two-Arm Randomised Trial

by Mark Liu, Sharon Kilbreath, Jasmine Yee, Jane Beith and Elizabeth Dylke

Cancers 2026, 18(2), 338; https://doi.org/10.3390/cancers18020338 - 21 Jan 2026

Viewed by 341

Abstract

Background/Objectives: Physical activity benefits women with metastatic breast cancer. Past trials are typically well-resourced and supervised, but home-based interventions may be preferable and more accessible. This pilot trial evaluated the feasibility and preliminary efficacy of a remotely delivered behaviour change intervention aiming to [...] Read more.

Background/Objectives: Physical activity benefits women with metastatic breast cancer. Past trials are typically well-resourced and supervised, but home-based interventions may be preferable and more accessible. This pilot trial evaluated the feasibility and preliminary efficacy of a remotely delivered behaviour change intervention aiming to increase physical activity for women with metastatic breast cancer. Methods: A 12-week, two-arm trial involved 20 women with metastatic breast cancer randomised 1:1 to a generic recommendation group or behaviour change group. Both groups received a physical activity recommendation, Fitbit^® watch, diary, and nine phone/video call sessions. The behaviour change group received individualised advice around physical activity benefits, motivation, barriers, and social support; the generic recommendation group completed a recurring symptom questionnaire. Feasibility outcomes were recruitment, retention and adherence rates. Acceptability was evaluated with a structured interview at trial completion. Preliminary efficacy outcomes included 5-day Actigraph wear, 6 min walk distance, 30 s sit-to-stands, and questionnaires for self-reported physical activity, quality-of-life, fatigue, behavioural factors, and patient-specific function. Results: Recruitment, retention, and adherence rates were 63% (n = 20/32), 80% (n = 16/20), and 76% (137/180 sessions), respectively. Participants across both groups reported that participation was acceptable, and their behaviour change was perceived as sustainable. Preliminary change scores for efficacy measures favoured the behaviour change group, except some quality-of-life and behavioural factor subscales. Conclusions: Participants were receptive to the trial, and feasibility and efficacy measures were positive. This indicates that a behaviour change intervention for unsupervised physical activity is acceptable and can be beneficial to women with metastatic breast cancer, warranting further exploration. Full article

(This article belongs to the Special Issue Exercise Interventions for People Living with Cancer: Advances in Knowledge and Implementation)

► Show Figures

Figure 1

21 pages, 1308 KB

Open AccessReview

Necessary, Legendary and Detrimental Components of Human Colorectal Organoid Culture Medium: Raising Awareness to Reduce Experimental Bugs

by Roberto Benelli

Cancers 2026, 18(2), 337; https://doi.org/10.3390/cancers18020337 - 21 Jan 2026

Viewed by 505

Abstract

The creation of a specific culture medium for colorectal organoids in 2011 heralded a new era in human primary cultures by enabling the indefinite expansion of normal and pathological epithelial organoids. The original formula has been used ever since, with only minor, lab-specific [...] Read more.

The creation of a specific culture medium for colorectal organoids in 2011 heralded a new era in human primary cultures by enabling the indefinite expansion of normal and pathological epithelial organoids. The original formula has been used ever since, with only minor, lab-specific modifications. The goal of culturing organoids from different tissues has relied on saving and propagating the pluripotent stem cell. The “magic bullet” and all its subsequent derivatives have pursued this goal. Consequently, agonist and antagonist signals are chronically activated in the organoid medium, forcing organoid cells (as well as any other co-cultured cellular model) into constrained signaling pathways. This extremely artificial condition is often overlooked in experimental approaches and may bias the results. Furthermore, some molecules in the organoid medium have unpredictable off-target effects that significantly impact the behavior and maturation of certain cell populations. Nicotinamide, gastrin and PGE2 inhibit immune responses. SB202190, A83-01 and vanadate (from advanced DMEM-F12) modify intracellular signaling. N-AcetylCysteine and Primocin modify the redox response and mitochondrial metabolism, respectively. Thus, the unintentional addition of these molecules to the organoid medium introduces biases under specific experimental settings. While the original organoid medium formula is the gold standard for propagating organoids in vitro, more focused, reliable conditions are necessary for specific organoid-based tests. Full article

(This article belongs to the Section Methods and Technologies Development)

► Show Figures

Figure 1

35 pages, 1506 KB

Open AccessReview

Targeting Monocytes and Their Derivatives in Ovarian Cancer: Opportunities for Innovation in Prognosis and Therapy

by Dharvind Balan, Nirmala Chandralega Kampan, Mohamad Nasir Shafiee, Magdalena Plebanski and Nor Haslinda Abd Aziz

Cancers 2026, 18(2), 336; https://doi.org/10.3390/cancers18020336 - 21 Jan 2026

Viewed by 567

Abstract

Ovarian cancer remains the most lethal gynaecological malignancy primarily due to late-stage diagnosis, high recurrence rate, and limited treatment efficacy. Current diagnostic tools, including imaging and serum markers, lack sufficient sensitivity and specificity for early detection. Increasing evidence highlights the critical role of [...] Read more.

Ovarian cancer remains the most lethal gynaecological malignancy primarily due to late-stage diagnosis, high recurrence rate, and limited treatment efficacy. Current diagnostic tools, including imaging and serum markers, lack sufficient sensitivity and specificity for early detection. Increasing evidence highlights the critical role of myeloid-derived immune cells within the tumour microenvironment in shaping ovarian cancer progression and therapy response. Monocytes and their derivatives are central regulators of immune suppression, chemoresistance, and metastatic dissemination in ovarian tumours. Their recruitment and polarisation are governed by several signalling pathways offering promising therapeutic targets. Strategies including monocyte depletion, TAM reprogramming, MDSC maturation, DC vaccines, and their synergistic use with chemotherapy or immune checkpoint inhibitors are being explored to restore anti-tumour immunity in ovarian cancer. Parallel to therapeutic potential, the lymphocyte-to-monocyte ratio and its reciprocal monocyte-to-lymphocyte ratio have also emerged as potential accessible and cost-effective prognostic tools that predict disease aggressiveness and survival in ovarian cancer. This review features the diagnostic, prognostic, and therapeutic significance of monocytes and their derivatives in ovarian cancer management and highlighting new opportunities for next-generation immunomodulatory therapies. Full article

(This article belongs to the Collection Women’s Cancers Risk: Breast Cancer, Ovarian Cancer and Endometrial Cancer)

► Show Figures

Figure 1

16 pages, 459 KB

Open AccessSystematic Review

First-Line Chemotherapy Regimens for Advanced and Metastatic Leiomyosarcoma: Doxorubicin vs. Gemcitabine—A Systematic Review

by Ilma Khan, Priyal Agarwal, Nassar El Assaad, Ravin Ratan and Elise F. Nassif Haddad

Cancers 2026, 18(2), 335; https://doi.org/10.3390/cancers18020335 - 21 Jan 2026

Viewed by 949

Abstract

Background: Leiomyosarcomas are an aggressive soft-tissue sarcoma that arise from smooth muscle, have a high metastatic potential and account for 10–20% of soft-tissue sarcomas. Despite decades of research, the first-line treatment remains unresolved due to the absence of direct comparative trials, heterogeneous [...] Read more.

Background: Leiomyosarcomas are an aggressive soft-tissue sarcoma that arise from smooth muscle, have a high metastatic potential and account for 10–20% of soft-tissue sarcomas. Despite decades of research, the first-line treatment remains unresolved due to the absence of direct comparative trials, heterogeneous study designs, and trade-offs between efficacy and toxicity. This systematic review evaluates the optimal therapeutic systemic chemotherapy regimens in the first-line setting, specifically gemcitabine- and doxorubicin-based regimens, including associated toxicities. Methods: A systematic search in MEDLINE (Ovid), Embase (Ovid), and Cochrane Library (Wiley) identified studies of first-line gemcitabine- or doxorubicin-based chemotherapy for leiomyosarcoma. The review protocol was registered in PROSPERO (CRD420261280028). Of the 3092 articles screened, 11 articles were eligible for inclusion, comprising results from 1225 patients. Eligible studies were in English and included ≥10 patients with advanced/metastatic leiomyosarcoma reporting on LMS-specific outcomes and no prior systemic therapy. This qualitative systematic review synthesizes prospective and retrospective evidence without quantitative meta-analysis. Results: The review included two phase 3 trials, six phase 2 trials, one phase 1b trial, and two retrospective studies. While there was no direct comparison in this setting, doxorubicin-based combinations consistently reported higher objective response rates, progression-free survival, and overall survival. The most favorable outcomes were observed in the LMS04 trial with doxorubicin plus trabectedin followed by surgery and trabectedin maintenance, yielding a median progression-free survival of 12 months, overall survival of 33 months, and objective response rate of 36%. This regimen also had the highest grade 3–4 toxicity. Conclusions: Doxorubicin-based regimens remain the most active first-line option for leiomyosarcoma, although treatment practices remain heterogeneous. Full article

(This article belongs to the Special Issue News and How Much to Improve in Management of Soft Tissue Sarcomas)

► Show Figures

Figure 1

16 pages, 1199 KB

Open AccessArticle

Percutaneous Microwave Ablation Preserves Renal Function with Similar Long Term Oncologic Outcomes Compared to Surgery for Clinical T1 Renal Cell Carcinoma

by Daniel F. Roadman, Daniel D. Shapiro, Arighno Das, Leslie W. Nelson, Paz Lotan, Michael C. Risk, Kyle A. Richards, Elizabeth L. Koehne, David F. Jarrard, Fred T. Lee, Jr., Glenn O. Allen, Edwarda Golden, Tim Ziemlewicz, James Louis Hinshaw and Edwin Jason Abel

Cancers 2026, 18(2), 334; https://doi.org/10.3390/cancers18020334 - 21 Jan 2026

Viewed by 326

Abstract

Background/Objectives: Percutaneous microwave (MW) ablation is a nephron sparing treatment for localized renal cell carcinoma (RCC). We compared perioperative, renal functional, and oncologic outcomes for clinical stage 1 RCC treated with MW ablation, PN, or RN. Methods: Adults with clinical T1 kidney masses [...] Read more.

Background/Objectives: Percutaneous microwave (MW) ablation is a nephron sparing treatment for localized renal cell carcinoma (RCC). We compared perioperative, renal functional, and oncologic outcomes for clinical stage 1 RCC treated with MW ablation, PN, or RN. Methods: Adults with clinical T1 kidney masses treated with MW ablation, PN, or RN from 2001–2025 were identified. Outcomes included: 90-day overall and major complication rate, 30-day readmission rate, length of hospital stay (LOS), change in renal function, local recurrence-free survival (LRFS), metastasis-free survival (MFS), and cancer-specific survival (CSS). Univariable and multivariable analyses evaluated outcomes adjusted for confounders. Results: A total of 2201 patients with renal masses ≤ 7 cm and no evidence of locally advanced or metastatic disease were treated with MW ablation (708), PN (729), or RN (764). MW ablation patients were older and more comorbid compared to both PN/RN, whereas RN patients had larger, higher-grade tumors. Ninety-day overall complications were lowest after MW ablation (8.9% vs. 20.3% PN, p < 0.001 and 8.9% vs. 19.9% RN, p < 0.001). LOS was shortest after MW ablation (median 1 day vs. 3 days PN/RN, p < 0.001 for each). Six-month eGFR decline was similar after MW ablation and PN (−5.2% and −4.7%, p = 0.84) but greater after RN (−32.9%, p < 0.001). Local recurrences were more common with MW ablation, with five-year LRFS 96.4% versus 99.7% for PN (p < 0.001). Five-year MFS (99.5% vs. 99.7%, p = 0.24) and CSS (99.3% vs. 99.7%, p = 0.71) did not differ between MW ablation and PN. Conclusions: Percutaneous MW ablation has comparable metastasis free and cancer specific survival with lower perioperative morbidity and comparable renal preservation to PN, despite worse baseline comorbidity and renal function. These findings support MW ablation as an effective nephron-sparing option for appropriately selected patients with clinical T1 RCC when performed at an experienced center. Full article

(This article belongs to the Special Issue Minimally Invasive Approaches in Urological Oncology: Current Trends and Innovations)

► Show Figures

Figure 1

8 pages, 223 KB

Open AccessOpinion

Does Cachexia Matter for Glioblastoma Multiforme?

by Ryan Kelly, Lydia Henderson and Ishan Roy

Cancers 2026, 18(2), 333; https://doi.org/10.3390/cancers18020333 - 21 Jan 2026

Viewed by 244

Abstract

Cachexia is a muscle-wasting syndrome that has a 50% overall prevalence across all cancers and is known to affect both survival and quality of life. However, its measurement, classification, and impact in individuals with primary brain tumors is unclear. Now, evidence is emerging [...] Read more.

Cachexia is a muscle-wasting syndrome that has a 50% overall prevalence across all cancers and is known to affect both survival and quality of life. However, its measurement, classification, and impact in individuals with primary brain tumors is unclear. Now, evidence is emerging that cachexia has a direct effect on both clinical and physical function outcomes for individuals with glioblastoma multiforme (GBM). Herein, we outline a standardized approach to the diagnosis of cachexia in the GBM population, incorporating several available clinical tools to ensure the link between clinical prognosis and quality of life. Full article

(This article belongs to the Special Issue Quality of Life in Patients with Brain Tumors)

10 pages, 246 KB

Open AccessArticle

Transition from Transrectal Systematic to Transperineal Lesion-Focused Prostate Biopsy: A Real-World Comparative Analysis

by Thibaut Long Depaquit, Federica Sordelli, Christopher Agüero, Arthur Peyrottes, Alessandro Uleri, Laurent Daniel, David Chemouni, Cyrille Bastide and Michael Baboudjian

Cancers 2026, 18(2), 332; https://doi.org/10.3390/cancers18020332 - 21 Jan 2026

Viewed by 221

Abstract

Background/Objectives: The transperineal (TP) approach has progressively replaced the transrectal (TR) approach for prostate biopsy because of its improved safety profile. However, its impact on the detection of clinically significant prostate cancer (csPCa), particularly within modern lesion-focused biopsy strategies that combine targeted and [...] Read more.

Background/Objectives: The transperineal (TP) approach has progressively replaced the transrectal (TR) approach for prostate biopsy because of its improved safety profile. However, its impact on the detection of clinically significant prostate cancer (csPCa), particularly within modern lesion-focused biopsy strategies that combine targeted and perilesional sampling, remains uncertain. We aimed to evaluate the real-world diagnostic impact of transitioning from a TR systematic-based biopsy strategy to a TP lesion-focused approach. Methods: We conducted a retrospective single-centre study including consecutive men who underwent image-guided prostate biopsy between 2018 and 2025. Only patients with a single MRI-visible lesion (PI-RADS ≥ 3) were included. Two biopsy strategies were compared: TR systematic biopsy (TR–SBx), combining targeted and systematic cores, and TP lesion-focused biopsy (TP–LFx), combining targeted and perilesional cores. The primary outcome was the detection of csPCa (Gleason Grade Group ≥ 2). Secondary outcomes included detection of Gleason Grade Group 1 cancer and negative biopsies. Inverse probability of treatment weighting (IPTW) based on a propensity score was applied to adjust for baseline differences. Doubly robust weighted logistic regression models were used, with predefined subgroup and sensitivity analyses. Results: Among 1032 included patients, 931 underwent TR–SBx and 101 TP–LFx. After restriction to the region of common support, 528 patients were retained for IPTW analyses. In the IPTW-adjusted analysis, TP–LFx was associated with higher csPCa detection compared with TR–SBx (adjusted odds ratio [OR] 2.52, 95% confidence interval [CI] 1.40–4.52; p = 0.002) and with lower detection of Gleason Grade Group 1 cancer (OR 0.50, 95% CI 0.27–0.92; p = 0.03). Subgroup analyses suggested a stronger association in patients with prior negative biopsy and in anterior or apical lesions. Conclusions: In routine clinical practice, transitioning from a transrectal systematic-based biopsy strategy to a transperineal lesion-focused approach was associated with improved detection of csPCa and reduced overdiagnosis. These findings support the consideration of transperineal, lesion-focused MRI-guided biopsy strategies in contemporary prostate cancer diagnostics. Full article

(This article belongs to the Special Issue New Trends in Urologic Oncology: Surgical Treatments, Robotics, Biomarkers, Diagnostic Tools, and Innovative Therapies)

15 pages, 950 KB

Open AccessReview

Molecular Insights into Helicobacter pylori-Induced Gastritis and Gastric Cancer

by Silvia Salvatori, Irene Marafini, Pasquale De Vico, Antonio Fonsi and Giovanni Monteleone

Cancers 2026, 18(2), 331; https://doi.org/10.3390/cancers18020331 - 21 Jan 2026

Viewed by 722

Abstract

Helicobacter pylori (H. pylori) is recognized as one of the most widespread and persistent bacterial infections globally, with a remarkable ability to colonize the human stomach. This pathogen is a major contributor to the development of gastric diseases, including gastric lymphoma [...] Read more.

Helicobacter pylori (H. pylori) is recognized as one of the most widespread and persistent bacterial infections globally, with a remarkable ability to colonize the human stomach. This pathogen is a major contributor to the development of gastric diseases, including gastric lymphoma and adenocarcinoma. The H. pylori infection triggers a complex pathogenic cascade within the gastric environment, characterized by prolonged inflammation and heightened oxidative stress, which fosters a milieu of immune dysregulation, where both innate and adaptive immune cells become activated inappropriately, thereby leading to epithelial injury and subsequent remodeling of the gastric tissue. As the infection persists, repeated cycles of inflammation and epithelial damage contribute to the development of epigenetic alterations, including changes in DNA methylation, histone modifications, and non-coding RNA expression, all of which render the gastric epithelium more susceptible to further aberrations, including dysplasia and cancer. In this article, we review the latest advances in understanding the molecular mechanisms of H. pylori-induced gastritis and its role in the progression of gastric cancer, offering new perspectives on the complex biology of this infection and its potential therapeutic implications for preventing the development of gastric malignancies. Full article

(This article belongs to the Section Cancer Immunology and Immunotherapy)

► Show Figures

Figure 1

22 pages, 5891 KB

Open AccessArticle

Two-Stage Microwave Hyperthermia Using Magnetic Nanoparticles for Optimal Chemotherapy Activation in Liver Cancer: Concept and Preliminary Tests on Wistar Rat Model

by Oliver Daniel Schreiner, Thomas Gabriel Schreiner, Lucian Miron and Romeo Cristian Ciobanu

Cancers 2026, 18(2), 330; https://doi.org/10.3390/cancers18020330 - 21 Jan 2026

Viewed by 367

Abstract

Background/Objectives: Liver cancer is among the most frequent poor-prognosis malignancies worldwide, with currently insufficient effective treatment. The two-stage microwave hyperthermia using magnetic nanoparticles is a modern technique designed to specifically target tumor tissues and facilitate chemotherapy activation, with promising results from fundamental [...] Read more.

Background/Objectives: Liver cancer is among the most frequent poor-prognosis malignancies worldwide, with currently insufficient effective treatment. The two-stage microwave hyperthermia using magnetic nanoparticles is a modern technique designed to specifically target tumor tissues and facilitate chemotherapy activation, with promising results from fundamental studies across various tumor types. The method consists of a first irradiation, performed before nano-assemblies administration. This is intended to sensitize the tumor by inducing a hyperthermic effect, leading to increasing blood supply, enhancing endothelial damage/permeation and inflammatory activation, with the final goal of improving the diffusion/retention of nano-assemblies in the tumor. Subsequently, the second microwave irradiation follows the injection in the hepatic artery and diffusion in the tumor of the activated nano-assemblies, to further determine a strong, but localized and focalized hyperthermic action. Nano-magnetic assemblies for hyperthermia accomplish the proposed chemo-thermal delivery, i.e., act per se on the tumor and also destabilize co-administered assemblies of nanoparticles loaded with chemotherapeutics, which would be consequently released locally in the most efficient way. This article aims to demonstrate the efficacy of this therapeutic approach in a rat liver model and its potential applicability in patients with liver tumors. Methods: Adult male Wistar rats were used to obtain liver samples, which were divided into three groups, each receiving a different hyperthermia protocol in terms of temperature (41–45 °C), duration, and co-administration of nanoparticles. Results: The most suitable exposure temperature for rat liver appears to be 42 °C, resulting in vacuolar degeneration lesions at the focal level. The effects of thermal conditioning do not appear to be homogeneous in the tested liver, and the controlling environment and methodology should be improved in the near future. The level of hepatic inflammation, as indicated by elevated interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α) levels, appears negligible under the current hyperthermia protocol. Conclusions: Two-stage microwave hyperthermia using magnetic nanoparticles is a promising therapeutic modality for liver cancer, with promising results from animal studies opening the way for further research in humans. Full article

(This article belongs to the Section Methods and Technologies Development)

► Show Figures

Figure 1

13 pages, 660 KB

Open AccessOpinion

Frontiers in Cell-Cycle-Targeting Therapies: Addressing the Heterogeneity of the Cancer Cell Cycle

by Ishaar P. Ganesan and Hiroaki Kiyokawa

Cancers 2026, 18(2), 329; https://doi.org/10.3390/cancers18020329 - 21 Jan 2026

Viewed by 530

Abstract

The cell division cycle machinery has been regarded as a promising therapeutic target for several decades. One of the most prominent milestones in the approach to targeting the cancer cell cycle was the development and approval of CDK4/6 inhibitors such as palbociclib, ribociclib, [...] Read more.

The cell division cycle machinery has been regarded as a promising therapeutic target for several decades. One of the most prominent milestones in the approach to targeting the cancer cell cycle was the development and approval of CDK4/6 inhibitors such as palbociclib, ribociclib, and abemaciclib. These small-molecule therapeutics have exhibited remarkable anti-cancer efficacy and have become primary choices for treating steroid receptor-positive breast cancer at multiple stages. This epoch-making success of cell-cycle-targeting drugs was followed by the development of small molecules to target other cell cycle-regulatory proteins, such as CDK2, CDK1, WEE1 kinase, Aurora kinases, and polo-like kinases, while therapeutic strategies to overcome resistance to CDK4/6 inhibitors have been pursued. In this article, we focus on heterogeneous vulnerabilities of cancers as consequences of various genetic and epigenetic alterations in the cell cycle-regulatory network, and we discuss how next-generation cell-cycle-targeting drugs currently in the developmental pipeline could exploit these heterogeneous vulnerabilities in the cancer cell cycle. We hope to provide a forward-looking perspective on directions for therapeutic cell-cycle targeting in the advent of personalized precision medicine. Full article

(This article belongs to the Special Issue Cancer Cell Vulnerabilities on Pathways Regulating the Cell Cycle)

► Show Figures

Figure 1

30 pages, 7385 KB

Open AccessReview

Spectrum of Biliary Lesions/Neoplasms in Hepatic Parenchyma with Reference to a Precursor of Small Duct-Type Intrahepatic Cholangiocarcinoma: Comprehensive Categorization into Three Groups

by Yasuni Nakanuma, Motoko Sasaki, Yuko Kakuda and Takuma Oishi

Cancers 2026, 18(2), 328; https://doi.org/10.3390/cancers18020328 - 21 Jan 2026

Viewed by 385

Abstract

Intrahepatic cholangiocarcinomas (iCCAs) are histologically subdivided into small duct-type (SD-iCCA) and large duct-type (LD-iCCA). LD-iCCA versus SD-iCCA may differ in the molecular/genetic profiles and oncogenesis, including precursor lesions. While several precursors, such as high-grade biliary intraepithelial neoplasm (BilIN) and intraductal papillary neoplasm of [...] Read more.

Intrahepatic cholangiocarcinomas (iCCAs) are histologically subdivided into small duct-type (SD-iCCA) and large duct-type (LD-iCCA). LD-iCCA versus SD-iCCA may differ in the molecular/genetic profiles and oncogenesis, including precursor lesions. While several precursors, such as high-grade biliary intraepithelial neoplasm (BilIN) and intraductal papillary neoplasm of bile duct (IPNB), have been proposed for LD-iCCA, the potential SD-iCCA precursors remain to be identified. Amid growing interests in the precursors of SD-iCCA, benign “biliary lesions/neoplasms developing in the hepatic parenchyma (BLNP)” such as von Meyenburg complexes (VMCs), bile duct adenomas (BDAs), and biliary adenofibroma (BAF), have been noted to determine whether they have the potential for precursor of SD-iCCA. Herein, these BLNPs were reviewed. BLNP can be classified into three categories. First, traditional VMC and BDA in normal livers which lack atypical features are categorized as “traditional BLNP”. Second, a constellation of several lesions such as VMC and BDA detectable in the background livers of SD-iCCA and in chronic liver disease (unusual VMC and BDA), VMC with dysplastic features, BDA located in the deep hepatic parenchyma, multiple BDA, BDA presenting the BRAF V600E mutation, and BAF harboring variable dysplasia or in situ carcinomas, which may include neoplastic lesions but do not show invasive growth, are categorized as “unusual/dysplastic BLNP”. Third, tubulocystic carcinoma with BAF-like features (AI-TCC) and SD-iCCA with ductal plate malformation (DPMP) which share overlapping features and show relatively good post-operative outcomes and retained features of VMC or DPM, and BDA and BAF, are categorized as “low-grade malignant BLNP”. While the first category is benign and may not be related to SD-iCCA, some of the second category may be related to SD-iCCA, and the third category is malignant and shows invasive growth. The latter two categories may form a common biliary tumorigenic spectrum involving BLNP. Precursors of SD-iCCA, if they exist, may be included in the second category, and the third category may represent unique carcinomas possibly associated with or followed by conventional SD-iCCA. In conclusion, this novel approach to categorize BLNPs into three categories guarantees further studies of precursors of and their progression to conventional SD-iCCA. Full article

(This article belongs to the Topic Hepatobiliary and Pancreatic Diseases: Novel Strategies of Diagnosis and Treatments—Second Edition)

► Show Figures

Figure 1

17 pages, 1351 KB

Open AccessReview

Integrated and Comprehensive Diagnostics: An Emerging Paradigm in Precision Oncology

by Kakoli Das, Jens Samol, Irfan Sagir Khan, Bernard Ho and Khoon Leong Chuah

Cancers 2026, 18(2), 327; https://doi.org/10.3390/cancers18020327 - 21 Jan 2026

Viewed by 251

Abstract

Recent advances in molecular pathology, driven by integrated and comprehensive diagnostic approaches, have significantly advanced precision oncology. By leveraging multiomics technologies, molecular pathology enables the simultaneous assessment of genomic alterations, transcriptomic profiles, proteomic activity, and metabolic states integrated with conventional pathological evaluation to [...] Read more.

Recent advances in molecular pathology, driven by integrated and comprehensive diagnostic approaches, have significantly advanced precision oncology. By leveraging multiomics technologies, molecular pathology enables the simultaneous assessment of genomic alterations, transcriptomic profiles, proteomic activity, and metabolic states integrated with conventional pathological evaluation to better explain tumour biology and behaviour. Large-scale international consortia, including The Cancer Genome Atlas (TCGA) and the Clinical Proteomic Tumour Analysis Consortium (CPTAC) have systematically demonstrated the value of harmonised multiomics analyses in defining tumour subtypes, uncovering functional dependencies, and generating clinically actionable insights. Evidence from coordinated precision oncology initiatives, such as the National Cancer Institute—Molecular Analysis for Therapy Choice (NCI-MATCH) trial further indicates that treatment strategies guided by molecular pathology profiling are associated with improved clinical outcomes, including progression-free survival in molecularly selected patient populations. Consequently, molecularly stratified treatment approaches are increasingly required in routine clinical practice to enable targeted therapies for selected tumour entities. Integration of molecular data with functional and clinical outcomes has further facilitated the detection of emerging mechanisms of therapeutic resistance and heterogeneous treatment responses. Importantly, studies have shown that reliance on genomic analysis alone is insufficient to achieve optimal targeted therapy, underscoring the need for multi-layered molecular interrogation. This review highlights the biological and clinical relevance of multiomics integration, emphasising its critical role in comprehensive morpho-molecular tumour assessment and functional analyses while providing clinicians with a practical framework for interpreting integrated molecular diagnostics and addressing the methodological and translational challenges that must be overcome to enable broader implementation of precision oncology in routine practice. Full article

(This article belongs to the Special Issue Molecular Pathology and Human Cancers)

► Show Figures

Figure 1

14 pages, 1010 KB

Open AccessArticle

Male Breast Cancer in Serbia: A 33-Year Retrospective Cohort Study of Genetic Predisposition, Clinicopathological Features, and Survival Outcomes

by Zorka Inić, Milan Žegarac, Ana Krivokuća, Ognjen Živković, Marko Buta, Nikola Vučić, Dobrica Stević, Anđela Milićević, Ivan Marković and Igor Đurišić

Cancers 2026, 18(2), 326; https://doi.org/10.3390/cancers18020326 - 21 Jan 2026

Viewed by 315

Abstract

Background/Objectives: Male breast cancer (MBC) is rare, accounting for less than 1% of all breast cancers. Given its low incidence, male breast cancer (MBC) remains understudied; this 33-year Serbian cohort was assessed for clinicopathological features, therapeutic approaches, genetic alterations, and survival. Methods [...] Read more.

Background/Objectives: Male breast cancer (MBC) is rare, accounting for less than 1% of all breast cancers. Given its low incidence, male breast cancer (MBC) remains understudied; this 33-year Serbian cohort was assessed for clinicopathological features, therapeutic approaches, genetic alterations, and survival. Methods: We retrospectively analyzed MBC patients diagnosed between 1991 and 2024 at the Institute for Oncology and Radiology of Serbia. Data included demographics, tumor characteristics, and stage, treatment, hormone receptor and HER2 status, Ki-67 index, genetic testing, and survival. Results: A total of 191 patients were identified (median age 66). Family history was negative in 91% and positive in 5.8%. T2 tumors were most frequent (36%), and 96% presented without metastasis. Mastectomy with axillary or sentinel lymph node dissection was performed in 78.5%. Neoadjuvant chemotherapy and radiotherapy were administered in 5.8% and 8.4%. Estrogen receptor positivity was 72%, progesterone receptor 88%, HER2 overexpression 11.0%, and triple-negative tumors 2.6% (40% with axillary involvement). High Ki-67 (≥15%) was recorded in 28.8%. Adjuvant chemotherapy, radiotherapy, and hormone therapy were given in 36%, 58%, and 68%. Among 37 genetically tested patients, seven had pathogenic variants (BRCA1, BRCA2, CHEK2, PALB2). Disease recurrence occurred in 30%. Median follow-up was 53 months. Median disease-free survival (DFS) was 82 months (1-, 2-, 5-, 10-year DFS: 87%, 73%, 57%, 39%). Median overall survival (OS) 131 months (1-, 2-, 5-, 10-year OS: 95%, 93%, 73%, 53%). Conclusions: This long-term cohort highlights the predominance of hormone-receptor positivity, the infrequency of germline mutations, and moderate survival rates, informing patient management and guiding future studies. Full article

(This article belongs to the Section Clinical Research of Cancer)

► Show Figures

Figure 1

26 pages, 742 KB

Open AccessArticle

Understanding the Experiences of Adolescents and Young Adults Diagnosed with Cancer During Higher Education—An Exploratory Interview Study

by Anke W. Boumans, Margo J. van Hartingsveldt, Angela G. E. M. de Boer, Maaike M. Brus, Floor M. Hoddenbagh-Bosdijk, Milou J. P. Reuvers, Jack D. Morgan, Martijn M. Stuiver and Olga Husson

Cancers 2026, 18(2), 325; https://doi.org/10.3390/cancers18020325 - 20 Jan 2026

Viewed by 298

Abstract

Background/Objectives: Adolescents and young adults (AYAs) with cancer often begin their careers later in life and are at risk of negative work-related outcomes. Research into and tailored support programs for AYAs diagnosed during higher education remain limited. An improved understanding of AYAs’ [...] Read more.

Background/Objectives: Adolescents and young adults (AYAs) with cancer often begin their careers later in life and are at risk of negative work-related outcomes. Research into and tailored support programs for AYAs diagnosed during higher education remain limited. An improved understanding of AYAs’ experiences is essential in guiding the development of age-appropriate support programs. This study explored the impact of cancer and the challenges AYAs face in educational participation and the transition to work. Methods: A qualitative study was conducted with thirteen AYAs diagnosed with cancer during higher education. Participants were interviewed using a semi-structured guide. In collaboration with patient experts as co-researchers, data were analyzed via thematic analysis. Results: Eight analytically derived themes reflected AYA students’ experiences: (1) Meaning and importance of education, (2) Reduced performance, (3) Recovery and expectations, (4) Interruption and delay, (5) Transition to work, (6) Disclosure, (7) Challenges related to the context of students, and (8) Experienced lack of support. The themes were clustered into four overarching thematic categories: Meaningful participation, Impact on performance, Academic progress and career transition, and Challenges in navigation. Conclusions: Our findings provide greater insight into the significance of educational participation for AYAs. AYA students encounter challenges stemming from both diagnosis-related changes in functioning and from contextual factors tied to their roles as students and new starters in the labor market. Navigating the healthcare, education, and social systems is complex and AYAs often lack adequate support when resuming their education or transitioning to work. Tailored support programs in healthcare and educational settings should be developed to help AYAs harness their strong motivation to resume studies, enter the labor market, and achieve their full potential. Full article

(This article belongs to the Special Issue Survivorship Following Childhood, Adolescent and Young Adult Cancer)

► Show Figures

Figure 1

16 pages, 745 KB

Open AccessArticle

Preoperative Cachexia as a Predictor of Postoperative Morbidity and a Target for Home-Based Prehabilitation in Resectable Gastric Cancer

by Vladimir Konstantinovich Lyadov, Tatiana Sergeevna Boldyreva, Alexander Yuryevich Gorshkov, Elena Vitalievna Zyatenkova, Anna Yurievna Ikonnikova, Mikhail Georgievich Chashchin and Vsevolod Nikolaevich Galkin

Cancers 2026, 18(2), 324; https://doi.org/10.3390/cancers18020324 - 20 Jan 2026

Viewed by 361

Abstract

Background: Gastric cancer (GC) is one of the most common malignancies, requires aggressive treatment, as has a high incidence of complications. The high prevalence of cachexia and comorbidity among GC patients has led to the development of the “prehabilitation” concept. We aimed to [...] Read more.

Background: Gastric cancer (GC) is one of the most common malignancies, requires aggressive treatment, as has a high incidence of complications. The high prevalence of cachexia and comorbidity among GC patients has led to the development of the “prehabilitation” concept. We aimed to investigate the prognostic value of cachexia in the “Western” patient population with resectable GC and to evaluate its utility as an indicator for a home-based prehabilitation program. Methods: This cohort study included 147 patients who underwent surgical treatment for GC from 2019 to 2023. A multivariable analysis was conducted to study the impact of cachexia on postoperative outcomes in 122 patients with resectable GC. The prehabilitation group included 25 patients with cachexia who underwent a 2-week-long multimodal prehabilitation program prior to surgery. The functional results, as well as the 30-day incidence of postoperative complications and 90-day mortality, were evaluated. Results: There were 76 (51.7%) patients with cachexia. Multivariate analysis revealed that cachexia was a significant predictor of all postoperative complications (OR = 5.48, 95% CI 1.85–18.39, p = 0.001), severe postoperative complications (OR = 15.87, 95% CI 3.05–131.81, p < 0.001) and surgical site infection (SSI) (OR = 8.03, 95% CI 1.89–49.09, p = 0.038). Patients in the prehabilitation group had a lower incidence of SSI than in the control group (8.3% vs. 23.5%, p = 0.049). Conclusions: Preoperative cachexia is a potentially modifiable predictor of complications after gastric cancer surgery, and its identification may help define high-risk patients for proactive multimodal prehabilitation. Full article

(This article belongs to the Special Issue Preoperative Optimisation in Patients Undergoing Cancer Surgery: 2nd Edition)

► Show Figures

Figure 1

11 pages, 547 KB

Open AccessReview

Zipalertinib—A Novel Treatment Opportunity for Non-Small Cell Lung Cancers with Exon 20 Insertions and Uncommon EGFR Mutations

by Wolfram C. M. Dempke, Klaus Fenchel and Niels Reinmuth

Cancers 2026, 18(2), 323; https://doi.org/10.3390/cancers18020323 - 20 Jan 2026

Viewed by 503

Abstract

Non-small cell lung cancer (NSCLC) represents over 80% of all lung cancer cases and still has a huge mortality worldwide. Targeting epidermal growth-factor receptor (EGFR) alterations with overall response rates of more than 80% has provided a paradigm shift in the treatment of [...] Read more.

Non-small cell lung cancer (NSCLC) represents over 80% of all lung cancer cases and still has a huge mortality worldwide. Targeting epidermal growth-factor receptor (EGFR) alterations with overall response rates of more than 80% has provided a paradigm shift in the treatment of NSCLC; however, NSCLC patients harbouring uncommon mutations and exon 20 insertions still have a dismal prognosis underscoring the urgent need to develop novel EGFR tyrosine kinase inhibitors (TKIs) with proven activity against these EGFR alterations. Zipalertinib is a newly developed oral, irreversible compound which is characterized by its unique pyrrolopyrimidine structure which discriminates this novel TKI from others. It is active against the classical mutations (i.e., del19, L858R) and some of the uncommon mutations (e.g., T790M, G719X, S768I, L861Q, but not C797S) and is predominantly active in NSCLC cells harbouring exon20ins. Zipalertinib is currently being extensively evaluated in several clinical NSCLC trials (REZILIENT 1–4) and has shown significant clinical activity in NSCLC patients with uncommon mutations, exon20ins, and in brain metastases (REZILIENT 3 trial). Moreover, zipalertinib in combination with platinum-based chemotherapy followed by zipalertinib monotherapy as first-line therapy is currently being evaluated in the pivotal, ongoing REZILIENT 3 randomized trial. In addition, the efficacy of zipalertinib is also studied in the adjuvant setting (REZILIENT 4 trial, stage IB-IIIA NSCLCs with exon20ins and uncommon mutations). The role and the integration of therapies targeting exon20ins or uncommon mutations into the first- and second-line treatment armamentarium for NSCLC patients is not yet fully established, and the therapeutic impact of monotherapies (e.g., sunvozertinib, firmonertinib) versus combinations with standard platinum-based chemotherapy (e.g., zipalertinib, amivantamab) currently still lacks robust evidence to further change the therapeutic landscape for these patients. Therefore, results from the ongoing trials are eagerly awaited and are expected to shed some light on these open questions. Full article

(This article belongs to the Special Issue Molecular Advances in Lung Cancer: From Pathogenesis to Precision Therapy (2nd Edition))

► Show Figures

Figure 1

14 pages, 2074 KB

Open AccessArticle

Is There a Role for Hepatobiliary Scintigraphy in Thermal Ablation of Hepatocellular Carcinoma?

by Niek Wijnen, Joep de Bruijne, Rutger C. G. Bruijnen, Emma Ruijs, Hugo W. A. M. de Jong, Marnix G. E. H. Lam and Maarten L. J. Smits

Cancers 2026, 18(2), 322; https://doi.org/10.3390/cancers18020322 - 20 Jan 2026

Viewed by 217

Abstract

Purpose: Hepatobiliary scintigraphy (HBS) provides quantitative assessment of (future remnant) liver function, aiding clinical decision-making for surgical resection and radioembolization of hepatocellular carcinoma (HCC). However, its role for thermal ablation remains unexplored. This pilot study aimed to explore the potential role of [...] Read more.

Purpose: Hepatobiliary scintigraphy (HBS) provides quantitative assessment of (future remnant) liver function, aiding clinical decision-making for surgical resection and radioembolization of hepatocellular carcinoma (HCC). However, its role for thermal ablation remains unexplored. This pilot study aimed to explore the potential role of HBS in guiding patient selection and risk stratification for thermal ablation. Methods: All HCC patients who underwent thermal ablation between January 2021 and August 2025 and had HBS performed prior to ablation were retrospectively reviewed. Ablated non-tumor liver volumes (i.e., volume of ablated healthy parenchyma) were quantified using 3D segmentation. Absolute ablated liver function (i.e., the proportion of total HBS-derived liver function ablated) was also assessed. Clinical outcomes included changes in clinical scores (e.g., Child–Pugh) and the occurrence of hepatic decompensation after ablation. Results: Nine patients (13 tumors) were included. Median global HBS-derived liver function was 3.2%/min/m² (range 1.6–6.8%/min/m²). Three patients developed hepatic decompensation > 3 months after ablation, unlikely related to thermal ablation itself. The patient with the lowest baseline function (1.6%/min/m²) tolerated ablation without hepatic decompensation. Median ablated non-tumor liver volume was 14.4 cm³ (range 3.1–46.7 cm³), corresponding to a median of 0.9% (range 0.2–3.6%) of total liver volume ablated per lesion. Median absolute ablated function was 0.05%/min/m² (range 0.02–0.21%/min/m²). Conclusions: Thermal ablation was feasible and well tolerated even in patients with severely impaired liver function. Routine pre-ablation HBS does not appear necessary for thermal ablation of HCC, as only a small percentage of total functional liver volume is ablated. Full article

(This article belongs to the Special Issue Tumor Suppressor and Targeted Therapy in Hepatocellular Carcinoma: From Diagnosis to Treatment (2nd Edition))

► Show Figures

Figure 1

35 pages, 4376 KB

Open AccessReview

Clinical Image-Based Dosimetry of Actinium-225 in Targeted Alpha Therapy

by Kamo Ramonaheng, Kaluzi Banda, Milani Qebetu, Pryaska Goorhoo, Khomotso Legodi, Tshegofatso Masogo, Yashna Seebarruth, Sipho Mdanda, Sandile Sibiya, Yonwaba Mzizi, Cindy Davis, Liani Smith, Honest Ndlovu, Joseph Kabunda, Alex Maes, Christophe Van de Wiele, Akram Al-Ibraheem and Mike Sathekge

Cancers 2026, 18(2), 321; https://doi.org/10.3390/cancers18020321 - 20 Jan 2026

Viewed by 891

Abstract

Actinium-225 (²²⁵Ac) has emerged as a pivotal alpha-emitter in modern radiopharmaceutical therapy, offering potent cytotoxicity with the potential for precise tumour targeting. Accurate, patient-specific image-based dosimetry for ²²⁵Ac is essential to optimize therapeutic efficacy while minimizing radiation-induced toxicity. Establishing a [...] Read more.

Actinium-225 (²²⁵Ac) has emerged as a pivotal alpha-emitter in modern radiopharmaceutical therapy, offering potent cytotoxicity with the potential for precise tumour targeting. Accurate, patient-specific image-based dosimetry for ²²⁵Ac is essential to optimize therapeutic efficacy while minimizing radiation-induced toxicity. Establishing a robust dosimetry workflow is particularly challenging due to the complex decay chain, low administered activity, limited count statistics, and the indirect measurement of daughter gamma emissions. Clinical single-photon emission computed tomography/computed tomography protocols with harmonized acquisition parameters, combined with robust volume-of-interest segmentation, artificial intelligence (AI)-driven image processing, and voxel-level analysis, enable reliable time-activity curve generation and absorbed-dose calculation, while reduced mixed-model approaches improve workflow efficiency, reproducibility, and patient-centred implementation. Cadmium zinc telluride-based gamma cameras further enhance quantitative accuracy, enabling rapid whole-body imaging and precise activity measurement, supporting patient-friendly dosimetry. Complementing these advances, the cerium-134/lanthanum-134 positron emission tomography in vivo generator provides a unique theranostic platform to noninvasively monitor ²²⁵Ac progeny redistribution, evaluate alpha-decay recoil, and study tracer internalization, particularly for internalizing vectors. Together, these technological and methodological innovations establish a mechanistically informed framework for individualized ²²⁵Ac dosimetry in targeted alpha therapy, supporting optimized treatment planning and precise response assessment. Continued standardization and validation of imaging, reconstruction, and dosimetry workflows will be critical to translate these approaches into reproducible, patient-specific clinical care. Full article

(This article belongs to the Section Cancer Therapy)

► Show Figures

Figure 1

16 pages, 1978 KB

Open AccessArticle

Oncological Outcomes and Genomic Features of Gastric-Type Endocervical Adenocarcinoma, the Most Aggressive and Common HPV-Independent Cervical Cancer

by Ming Du, Zhen Zheng, Peiyao Lu, Weidi Wang, Dongyan Cao, Jiaxin Yang, Ming Wu, Lingya Pan, Xiaowei Xue, Wenze Wang, Fang Jiang and Yang Xiang

Cancers 2026, 18(2), 320; https://doi.org/10.3390/cancers18020320 - 20 Jan 2026

Viewed by 285

Abstract

Background/Objectives: In order to develop a comprehensive understanding of gastric-type endocervical adenocarcinoma (GEA), an increasingly prevalent HPV-independent cervical cancer, we summarized clinicopathological information and performed prognostic analysis. Methods: A total of 182 patients diagnosed with GEA at our center during the [...] Read more.

Background/Objectives: In order to develop a comprehensive understanding of gastric-type endocervical adenocarcinoma (GEA), an increasingly prevalent HPV-independent cervical cancer, we summarized clinicopathological information and performed prognostic analysis. Methods: A total of 182 patients diagnosed with GEA at our center during the period 2014–2025 were included in this study. Nineteen GEA cases, 6 HPV-independent non-GEA cases, 59 HPV-associated usual endocervical adenocarcinoma cases, and 66 squamous cell carcinoma cases from online database were also included. Results: Vaginal bleeding (39.56%) and watery discharge (35.16%) were the most common symptoms. As many as 21.43% of patients had no specific complaints, and 80% of GEA showed no distinct mass through gynecological examination. A total of 64% of GEA were stage IIB–IV at diagnosis, with a 5-year survival of 41% versus 85% for stage I–IIA (p < 0.05). The rate of lymphovascular space invasion (LVSI), lymph node metastasis, and ovarian metastasis were 49.64%, 42.00%, and 29.29%, respectively. The 5-year survival and recurrence rates after primary therapy were 57% and 23%, respectively. For GEA treatment, surgery might be associated with improved overall survival for the population at stage III–IV. Survival analysis identified deep infiltration depth (≥2/3), a maximum diameter of the tumor (MDOT) of ≥3 cm, and ovary metastasis as potential indicators of worse OS and PFS for whole patients. Additionally, ovary metastasis indicated poor PFS and OS for stage I–II. Genomic information TP53 mutation, PTEN deletion and STK11 mutation might be the most prevalent genomic alterations. Conclusions: These findings indicated GEA as an aggressive cervical cancer, with high rate of lymph node metastasis, high recurrence rate and short 5-year survival. Ovary metastasis reflected advanced disease burden and surgery might be associated with improved survival in advanced stage. For genomic information, GEA showed genetic heterogeneity and a low level of genomic instability. Full article

(This article belongs to the Section Cancer Pathophysiology)

► Show Figures

Graphical abstract

13 pages, 537 KB

Open AccessArticle

HDR Brachytherapy in the Treatment of Skin Kaposi Sarcoma: A Mono-Institutional Series

by Bianca Santo, Elisa Ciurlia, Maria Cristina Barba, Elisa Cavalera, Rosa Coppola, Paola De Franco, Sara De Matteis, Giuseppe Di Paola, Angela Leone, Antonella Papaleo, Donatella Russo, Dino Rubini, Giuseppe Rubini and Angela Sardaro

Cancers 2026, 18(2), 319; https://doi.org/10.3390/cancers18020319 - 20 Jan 2026

Viewed by 267

Abstract

Background: Kaposi sarcoma (KS) is a multifocal, angioproliferative neoplasm strongly associated with human herpesvirus-8 infection. Radiotherapy(RT) is a well established treatment due to the intrinsic radiosensitivity of KS lesions. High-dose-rate contact brachytherapy allows precise dose delivery with optimal sparing of surrounding tissues; however, [...] Read more.

Background: Kaposi sarcoma (KS) is a multifocal, angioproliferative neoplasm strongly associated with human herpesvirus-8 infection. Radiotherapy(RT) is a well established treatment due to the intrinsic radiosensitivity of KS lesions. High-dose-rate contact brachytherapy allows precise dose delivery with optimal sparing of surrounding tissues; however, its application in KS remains poorly documented. Methods: We conducted a retrospective analysis of 10 patients with histologically confirmed KS treated with c-HDR-BRT between June 2010 and June 2023. A total of 40 cutaneous lesions were treated using Leipzig applicators with hypofractionated regimens: 10 Gy in 1 fraction, 20 Gy in 2 fractions, or 30 Gy in 3 fractions. Treatment parameters were individualized based on lesion size and location. Local control (LC), overall survival (OS), disease-specific survival (DSS), and toxicity (graded by the RTOG criteria) were evaluated. Follow-up assessments were performed every four months during the first year and annually thereafter. Results: At a median follow-up of 10.3 years, the 2-year LC, OS, and DSS rates were 100%. Complete response was achieved in 62.5% of lesions, with a partial response observed in 37.5%. Grade 1–2 acute skin toxicities were recorded in 55% of treated lesions, while grade 3 toxicity occurred in a single case (2.5%) and was managed conservatively. The hypofractionated schedule significantly improved patient compliance, particularly in those with multiple lesions requiring sequential irradiation. Conclusions: Our long-term institutional experience supports c-HDR-BRT as a feasible and well tolerated local treatment option for the management of KS, providing favorable long-term local outcomes. These results support the inclusion of c-HDR-BRT in the multidisciplinary treatment of KS, warranting further prospective evaluation. Full article

(This article belongs to the Section Cancer Therapy)

► Show Figures

Figure 1

Journal Menu

Journal Browser

Cancers, Volume 18, Issue 2 (January-2 2026) – 170 articles

Further Information

Guidelines

MDPI Initiatives

Follow MDPI