Cancers

14 pages, 886 KiB

Open AccessArticle

Correlations Between Mammographic Breast Density and Outcomes After Neoadjuvant Chemotherapy in Patients with Locally Advanced Breast Cancer

by Veenoo Agarwal, Lisa Spalding, Hilary Martin, Ellie Darcey, Jennifer Stone and Andrew Redfern

Cancers 2025, 17(13), 2214; https://doi.org/10.3390/cancers17132214 - 1 Jul 2025

Abstract

Introduction: An inverse association between high mammographic breast density (MBD) and pathologic complete response (pCR) following neoadjuvant chemotherapy (NAC) for early breast cancer (EBC) has been reported. However, the relationship of MBD to relapse-free (RFS) and breast cancer-specific survival (BCSS) is unexplored. This [...] Read more.

Introduction: An inverse association between high mammographic breast density (MBD) and pathologic complete response (pCR) following neoadjuvant chemotherapy (NAC) for early breast cancer (EBC) has been reported. However, the relationship of MBD to relapse-free (RFS) and breast cancer-specific survival (BCSS) is unexplored. This study aims to validate the relationship between MBD and NAC pCR in EBC and to assess correlations with RFS and BCSS. Materials & Methods: MBD was measured on contralateral mammograms in 127 women before NAC using Cumulus software. The percent dense area was correlated with patient and tumour characteristics, pCR, RFS and BCSS. Results: Mean MBD was higher in relapsing patients (p = 0.041) but did not vary by pCR or BC-deaths. As a dichotomous variable, no difference was seen between high and low MBD cohorts for pCR (17.5 vs. 25.0%, p = 0.15), BC relapse (38 vs. 30%, p = 0.15) or BC death (32 vs. 25%, p = 0.20). A planned analysis by body mass index (BMI) demonstrated high MBD associated with lower pCR (0% vs. 28.1%, p = 0.036) and trends for higher relapse (56% vs. 28%, p = 0.063) and BC deaths (56 vs. 28%, (p = 0.071)) in obese patients. No relationship was observed in non-obese patients. Conclusion: Obesity and high MBD may interact to cause chemoresistance. Further research in these patients is warranted. Full article

(This article belongs to the Special Issue New Insights in Mammographic Density in Breast Cancer Risk, Screening and Detection)

16 pages, 2433 KiB

Open AccessArticle

Perioperative and Oncological Outcome in Patients Undergoing Curative-Intent Liver Resection for Cholangiocarcinoma in the Context of Osteopenia

by Franziska A. Meister, Katharina Joechle, Philipp Tessmer, Esref Belger, Anjali A. Roeth, Oliver Beetz, Felix Oldhafer, Jan Bednarsch, Ulf P. Neumann, Carolin V. Schneider, Robert Siepmann, Iakovos Amygdalos, Florian W. R. Vondran and Zoltan Czigany

Cancers 2025, 17(13), 2213; https://doi.org/10.3390/cancers17132213 - 1 Jul 2025

Abstract

Background: Cholangiocarcinoma (CCA) of the liver is a highly aggressive cancer that arises from malignant cells in the bile ducts. Radical surgery remains the only curative option, but major liver resection carries high perioperative risks. This study investigates the predictive value of [...] Read more.

Background: Cholangiocarcinoma (CCA) of the liver is a highly aggressive cancer that arises from malignant cells in the bile ducts. Radical surgery remains the only curative option, but major liver resection carries high perioperative risks. This study investigates the predictive value of preoperative bone mineral density (BMD), measured via CT, for perioperative complications, mortality, and long-term outcomes. Methods: The analysis included 202 patients who underwent curative-intent surgery for intrahepatic cholangiocarcinoma (iCCA; n = 97) or perihilar cholangiocarcinoma (pCCA; n = 105) between 2010 and 2019. Preoperative bone mineral density (BMD) was assessed using computed tomography segmentation at the level of the 12th thoracic vertebra. Osteopenia was defined according to established cutoffs. Results: Osteopenia was highly prevalent in both iCCA (53/97, 54%) and pCCA (54/105, 51%) subcohorts. Patients suffering from osteopenia were significantly older than those without (71.1 [62–76.6] years vs. 61.3 [52.9–69.2] years; p < 0.001). Alteration in BMD did not demonstrate a significant prognostic effect in terms of perioperative morbidity (Mann–Whitney U; comprehensive complication index—CCI: 34 [9–56] vs. 40 [21–72] p = 0.185; iCCA: p = 0.803; pCCA: p = 0.165). The median overall survival in our cohort was 19 [14–25] months. Patients with osteopenia did not exhibit a significantly different overall survival compared to those with normal bone mineral density (log-rank p = 0.234). Conclusions: In contrast to our previous observations in other oncological patient cohorts, osteopenia alone had no significant negative impact on clinical outcomes in our large European cohort of patients undergoing curative-intent surgery for CCA. To validate these findings, further prospective studies are warranted. Full article

(This article belongs to the Special Issue Clinical Surgery for Hepato-Pancreato-Biliary (HPB) Cancer)

31 pages, 5480 KiB

Open AccessArticle

The Impact of Peroxiredoxin 3 on Molecular Testing, Diagnosis, and Prognosis in Human Pancreatic Ductal Adenocarcinoma

by Anna Kakehashi, Shugo Suzuki, Yusaku Nishidoi, Atsushi Hagihara, Hiroko Ikenaga, Masayuki Shiota, Guiyu Qiu, Ikue Noura, Yuko Kuwae, Arpamas Vachiraarunwong, Masaki Fujioka, Min Gi, Norifumi Kawada and Hideki Wanibuchi

Cancers 2025, 17(13), 2212; https://doi.org/10.3390/cancers17132212 - 1 Jul 2025

Abstract

Background/Objective: Pancreatic ductal adenocarcinoma (PDAC) is one of the leading causes of cancer death and tumors with an extremely poor prognosis. In the present study, novel biomarker candidates useful for the early diagnosis and prognosis of human invasive PDAC were investigated. Methods: Biomarker [...] Read more.

Background/Objective: Pancreatic ductal adenocarcinoma (PDAC) is one of the leading causes of cancer death and tumors with an extremely poor prognosis. In the present study, novel biomarker candidates useful for the early diagnosis and prognosis of human invasive PDAC were investigated. Methods: Biomarker candidates were first selected based on the proteomic/bioinformatic and clinico-pathological analyses of 10 and 100 patients with PDAC, respectively, operated at Osaka Metropolitan University Hospital (Exp. 1). Next, the expression and secretion of the target protein and its EV mRNA were investigated in pancreatic cancer cells in vitro and in a Balb/c nude mouse model. In addition, the protein and EV mRNA levels of candidate molecules were measured in the blood serum of 36 PDAC and 10 IPMN patients, and diagnostic significance was assessed (Exp. 2). Results: A significant elevation of peroxiredoxin 3 (PRX3), a mitochondrial matrix protein, was found in PDAC via LC-Ms/Ms analysis. In Exp. 1, PRX3 overexpression was found in PDAC and PanIN lesions and was associated with a tumor infiltrative growth pattern (INFc) and poor overall 1-year patient survival. The prognostic value was significantly improved when PRX3 was combined with serum SPan-1 and DUPAN-2 markers in survival analyses. Furthermore, the PRX3 protein and its extracellular vesicle (EV: exosome and oncosome)-incorporated mRNA were secreted at detectable levels from PANC-1, MIAPaCa-2, and SW1990 cells into the blood of Balb/c nude mice bearing tumors. The overexpression of PRX3 was positively correlated with that of cancer stem cell marker CD44 variant 9 (CD44v9), P-Nrf2, and FOXO3a, as well as the generation of reactive oxygen species. In Exp. 2, a significant increase in PRX3 protein and EV mRNA was detected in the blood serum of PDAC subjects compared to IPMN patients and healthy controls. Significantly higher PRX3 protein levels were found in the IPMN group. The elevation of PRX3 EV mRNA was significantly associated with poor patient survival. Conclusions: These results indicate that PRX3 may become a novel early biomarker for PDAC diagnosis and prognosis. Full article

(This article belongs to the Special Issue Diagnosis, Treatment and Prevention of Gastrointestinal Cancer (2nd Edition))

17 pages, 4381 KiB

Open AccessArticle

Multivariate Framework of Metabolism in Advanced Prostate Cancer Using Whole Abdominal and Pelvic Hyperpolarized ¹³C MRI—A Correlative Study with Clinical Outcomes

by Hsin-Yu Chen, Ivan de Kouchkovsky, Robert A. Bok, Michael A. Ohliger, Zhen J. Wang, Daniel Gebrezgiabhier, Tanner Nickles, Lucas Carvajal, Jeremy W. Gordon, Peder E. Z. Larson, John Kurhanewicz, Rahul Aggarwal and Daniel B. Vigneron

Cancers 2025, 17(13), 2211; https://doi.org/10.3390/cancers17132211 - 1 Jul 2025

Abstract

Background: Most of the existing hyperpolarized (HP) ¹³C MRI analyses use univariate rate maps of pyruvate-to-lactate conversion (k_PL), and radiomic-style multiparametric models extracting complex, higher-order features remain unexplored. Purpose: To establish a multivariate framework based on whole abdomen/pelvis HP ¹³ [...] Read more.

Background: Most of the existing hyperpolarized (HP) ¹³C MRI analyses use univariate rate maps of pyruvate-to-lactate conversion (k_PL), and radiomic-style multiparametric models extracting complex, higher-order features remain unexplored. Purpose: To establish a multivariate framework based on whole abdomen/pelvis HP ¹³C-pyruvate MRI and evaluate the association between multiparametric features of metabolism (MFM) and clinical outcome measures in advanced and metastatic prostate cancer. Methods: Retrospective statistical analysis was performed on 16 participants with metastatic or local-regionally advanced prostate cancer prospectively enrolled in a tertiary center who underwent HP-pyruvate MRI of abdomen or pelvis between November 2020 and May 2023. Five patients were hormone-sensitive and eleven were castration-resistant. GMP-grade [1-¹³C]pyruvate was polarized using a 5T clinical-research DNP polarizer, and HP MRI used a set of flexible vest-transmit, array-receive coils, and echo-planar imaging sequences. Three basic metabolic maps (k_PL, pyruvate summed-over-time, and mean pyruvate time) were created by semi-automatic segmentation, from which 316 MFMs were extracted using an open-source, radiomic-compliant software package. Univariate risk classifier was constructed using a biologically meaningful feature (k_PL,median), and the multivariate classifier used a two-step feature selection process (ranking and clustering). Both were correlated with progression-free survival (PFS) and overall survival (OS) (median follow-up = 22.0 months) using Cox proportional hazards model. Results: In the univariate analysis, patients harboring tumors with lower-k_PL,median had longer PFS (11.2 vs. 0.5 months, p < 0.01) and OS (NR vs. 18.4 months, p < 0.05) than their higher-k_PL,median counterparts. Using a hypothesis-generating, age-adjusted multivariate risk classifier, the lower-risk subgroup also had longer PFS (NR vs. 2.4 months, p < 0.002) and OS (NR vs. 18.4 months, p < 0.05). By contrast, established laboratory markers, including PSA, lactate dehydrogenase, and alkaline phosphatase, were not significantly associated with PFS or OS (p > 0.05). Key limitations of this study include small sample size, retrospective study design, and referral bias. Conclusions: Risk classifiers derived from select multiparametric HP features were significantly associated with clinically meaningful outcome measures in this small, heterogeneous patient cohort, strongly supporting further investigation into their prognostic values. Full article

(This article belongs to the Special Issue Prostate Cancer: Molecular Imaging and Magnetic Resonance Imaging (MRI))

► Show Figures

Figure 1

10 pages, 717 KiB

Open AccessCommunication

Expression Profiles of Co-Inhibitory Receptors in Non-Urothelial Bladder Cancer: Preclinical Evidence for the Next Generation of Immune Checkpoint Inhibitors

by Severin Rodler, Stephan T. Ledderose, Raphaela Waidelich, Jakob Kohler, Andrea Sendelhofert, Jozefina Casuscelli, Gerald Schulz, Christian G. Stief and Lennert Eismann

Cancers 2025, 17(13), 2210; https://doi.org/10.3390/cancers17132210 - 1 Jul 2025

Abstract

Immune checkpoint inhibition is a cornerstone of bladder cancer therapy, but its efficacy in non-urothelial subtypes of bladder cancer is limited, and the prognosis remains poor. Therefore, we investigated the potential of the immune checkpoint molecules TIM-3, TIGIT, and LAG-3 in squamous-cell carcinoma [...] Read more.

Immune checkpoint inhibition is a cornerstone of bladder cancer therapy, but its efficacy in non-urothelial subtypes of bladder cancer is limited, and the prognosis remains poor. Therefore, we investigated the potential of the immune checkpoint molecules TIM-3, TIGIT, and LAG-3 in squamous-cell carcinoma (SCC) and adenocarcinoma (ADENO) of the urinary bladder. Tumor-infiltrating lymphocytes (TILs) showed a high expression of TIM-3 and TIGIT in both SCC and ADENO, while LAG-3-positive TILs were absent in ADENO and present in 46% of SCC. Quantitative analysis revealed age-independent expression of TIM-3 in SCC (r = −0.001, p = 0.997) and ADENO (r = 0.135, p = 0.549), with increasing age correlating with higher expression of TIGIT (r = 0.157, p = 0.242) and LAG-3 (0.106, p = 0.436) in the SCC cohort and of TIGIT (r = 0.276, p = 0.214) in the ADENO cohort. Male patients showed increased TIGIT scores in ADENO (p < 0.01). Of note, a high infiltration of TIM-3-TILs (p = 0.048) correlated with worse progression-free survival in SCC. These results highlight the differential expression of co-inhibitory receptors in non-urothelial bladder cancer subtypes and provide preclinical evidence for new therapeutic targets. Biomarker testing prior to clinical trials is essential for identifying the most suitable patients for targeted immunotherapy. Full article

(This article belongs to the Special Issue New Insights into Urologic Oncology)

► Show Figures

Figure 1

20 pages, 336 KiB

Open AccessReview

End-of-Life Cancer Care Interventions for Racially and Ethnically Diverse Populations in the USA: A Scoping Review

by Carolyn J. Yee, Aashritha Penumudi, Terri Lewinson and Inas S. Khayal

Cancers 2025, 17(13), 2209; https://doi.org/10.3390/cancers17132209 - 1 Jul 2025

Abstract

Introduction: Racial and ethnic disparities in end-of-life (EOL) cancer care persist, leading to lower rates of advance care planning (ACP), reduced access to palliative care, and poorer patient outcomes for minority populations. While previous research has documented these inequities, less is known [...] Read more.

Introduction: Racial and ethnic disparities in end-of-life (EOL) cancer care persist, leading to lower rates of advance care planning (ACP), reduced access to palliative care, and poorer patient outcomes for minority populations. While previous research has documented these inequities, less is known about the specific interventions developed to address them, necessitating a comprehensive review of existing strategies aimed at improving EOL care for racial and ethnic populations. The objective of this scoping review is to examine the extent and characteristics of interventions and their outcomes designed to address racial and ethnic disparities in EOL cancer care in the United States. Methods: A comprehensive search of EOL cancer care interventions for minority populations was conducted in Ovid MEDLINE, CINAHL with Full Text (EBSCOhost), and Scopus (Elsevier) in September 2024. Two independent reviewers screened titles, abstracts, and full texts following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) guidelines, with inclusion limited to studies conducted in the US and published in English. Results: Of 3104 screened studies, 10 met the inclusion criteria. Participants enrolled were only from Latino (n = 6 studies) or Black (n = 4 studies) populations. We identified four types of interventions, including communication skills for patients, caregivers, researchers, and clinicians (n = 2), education programs for patients (n = 1), navigation and support programs for patients and caregivers (n = 3), and training programs for health workers and community leaders (n = 4). The most effective interventions were those that addressed linguistic barriers, integrated cultural values, and involved trusted community figures. Faith-based models were particularly successful among African American patients, while bilingual navigation and family-centered ACP interventions had the greatest impact in Latino populations. Conclusions: This review highlights (1) the importance of culturally tailored interventions for specific minority populations and (2) the limited number of such interventions, which primarily target only the largest minority groups. Full article

(This article belongs to the Special Issue The Impact of Community Context and Cancer Disparities)

► Show Figures

Figure 1

12 pages, 2407 KiB

Open AccessArticle

Identification of Deregulated Proteins in Mutated BRCA1/2 Breast and Ovarian Cancers for Vectorized Biologics

by Adrián Sanvicente, Cristina Nieto-Jiménez, Esther Cabañas Morafraile, Cristina Díaz-Tejeiro, Vanesa García Barberán, Pedro Pérez Segura, Győrffy Balázs and Alberto Ocaña

Cancers 2025, 17(13), 2208; https://doi.org/10.3390/cancers17132208 - 1 Jul 2025

Abstract

Background: Administration of PARP inhibitors against breast and ovarian cancers with BRCA1 and BRCA2 mutations has shown clinical benefits in patients. However, these agents are also toxic and have a narrow therapeutic index. Objectives: In this work, we aimed to identify membrane proteins [...] Read more.

Background: Administration of PARP inhibitors against breast and ovarian cancers with BRCA1 and BRCA2 mutations has shown clinical benefits in patients. However, these agents are also toxic and have a narrow therapeutic index. Objectives: In this work, we aimed to identify membrane proteins that are specifically upregulated in these cancers. Methods: We interrogated public datasets to analyze genes upregulated or downregulated when these mutations were present, compared with wild-type cancers. Surface protein expression and functional annotation analyses were also performed. Results: In breast cancer, we identified 11 upregulated and 44 downregulated transcripts in BRCA1-mut, while 10 upregulated and 57 downregulated transcripts were identified in BRCA2-mut cancers. In ovarian cancer, 79 transcripts were upregulated and 123 were downregulated in BRCA1-mut cancers, while five were upregulated and seven were downregulated in BRCA2-mut tumors. Regarding the biological function related to these genes, in BRCA1-mutated ovarian cancers, the main functions of upregulated genes included MHC assembly or regulation of the interferon gamma pathway; in BRCA2-mut ovarian cancers, regulation of phosphorylation and signaling; in BRCA1-mut breast cancers, cell damage repair and angiogenesis; and finally, in BRCA2-mut breast cancers, cytokine production and T-cell migration. Genes expressed in the surface membrane or extracellular matrix and related to patient outcomes included B3GNT7 and CTSV in BRCA2-mut breast cancers, exhibiting detrimental prognoses. CD6, CXCL9, and CXCL13 were associated with favorable outcomes in BRCA1-mutant ovarian cancers. The last three genes were also correlated with the infiltration of effector T cells and dendritic cells in ovarian tumors. Conclusions: In summary, we identified deregulated candidate genes that could be used as therapeutic targets. Full article

(This article belongs to the Section Tumor Microenvironment)

► Show Figures

Graphical abstract

15 pages, 2051 KiB

Open AccessArticle

Comparison of the Diagnostic Efficiency of Mediastinal Lymph Node Endobronchial and Endoesophageal Ultrasound with Transcervical Extended Mediastinal Lymphadenectomy in Operable Non-Small Cell Lung Cancer

by Michal Wilkojc, Pawel Gwozdz, Sylweriusz Kosinski, Juliusz Pankowski, Artur Szlubowski, Aleksandra Kiszka-Wilkojc, Wojciech Czajkowski, Robert Kwiatkowski and Marcin Zielinski

Cancers 2025, 17(13), 2207; https://doi.org/10.3390/cancers17132207 - 1 Jul 2025

Abstract

Objectives: The aim of the study was to compare the diagnostic efficiency between combined endobronchial ultrasound (EBUS)/endoesophageal ultrasound (EUS) and transcervical extended mediastinal lymphadenectomy (TEMLA) for preoperative staging of mediastinal lymph nodes in non-small cell lung cancer (NSCLC). Material and Methods: [...] Read more.

Objectives: The aim of the study was to compare the diagnostic efficiency between combined endobronchial ultrasound (EBUS)/endoesophageal ultrasound (EUS) and transcervical extended mediastinal lymphadenectomy (TEMLA) for preoperative staging of mediastinal lymph nodes in non-small cell lung cancer (NSCLC). Material and Methods: Between June 2011 and December 2017, a single-institution prospective randomized trial was conducted, and 250 patients with cytologically confirmed NSCLC, clinical stages cI–IIIA, were included. Positron emission tomography/computed tomography (PET/CT) was performed in all patients. After exclusions, 204 patients were randomized into the EBUS/EUS or TEMLA arms. Patients without N2/N3 metastases after mediastinal staging underwent surgery. The diagnostic yield and complication rates of the EBUS/EUS and TEMLA groups were compared. Results: There were 103 patients in the EBUS/EUS group, and N2 metastases were found in nine cases (8.7%). Ninety-four patients underwent surgery; in six cases, previously unsuspected N2 metastases were revealed. One hundred and one patients were randomized to the TEMLA group, which detected N2/N3 metastases in 15 cases (15.1%). Three patients were not operated on due to postoperative complications following TEMLA. Eighty-three patients underwent surgery, and a single N2 metastatic nodule was detected in one case. The diagnostic sensitivity, specificity, accuracy, PPV, and NPV were 94%, 100%, 99%, 100%, and 99% for TEMLA, respectively, and 60%, 100%, 94%, 100%, and 94% for EBUS/EUS, respectively. There was a significant difference in sensitivity (60% vs. 94%) between the EBUS/EUS and TEMLA groups in favor of the TEMLA group. Postoperative complications occurred in 6/101 (6%) patients after TEMLA, while no complications were observed in the EBUS/EUS group. Conclusions: TEMLA demonstrated superior sensitivity for detecting N2/3 disease compared to EBUS/EUS in terms of diagnostic performance for mediastinal staging of cI–IIIA NSCLC. Due to its more invasive nature, TEMLA was associated with a higher number of complications compared with EBUS/EUS. Full article

(This article belongs to the Special Issue Surgical Management of Non-Small Cell Lung Cancer)

► Show Figures

Figure 1

17 pages, 900 KiB

Open AccessArticle

Detection Rates of Prostate Cancer Across Prostatic Zones Using Freehand Single-Access Transperineal Fusion Biopsies

by Filippo Carletti, Giuseppe Reitano, Eleonora Martina Toffoletto, Arianna Tumminello, Elisa Tonet, Giovanni Basso, Martina Bruniera, Anna Cacco, Elena Rebaudengo, Giorgio Saggionetto, Giovanni Betto, Giacomo Novara, Fabrizio Dal Moro and Fabio Zattoni

Cancers 2025, 17(13), 2206; https://doi.org/10.3390/cancers17132206 - 30 Jun 2025

Abstract

Background/Objectives: It remains unclear whether certain areas of the prostate are more difficult to accurately sample using MRI/US-fusion-guided freehand single-access transperineal prostate biopsy (FSA-TP). The aim of this study was to evaluate the detection rates of clinically significant (cs) and clinically insignificant [...] Read more.

Background/Objectives: It remains unclear whether certain areas of the prostate are more difficult to accurately sample using MRI/US-fusion-guided freehand single-access transperineal prostate biopsy (FSA-TP). The aim of this study was to evaluate the detection rates of clinically significant (cs) and clinically insignificant (ci) prostate cancer (PCa) in each prostate zone during FSA-TP MRI-target biopsies (MRI-TBs) and systematic biopsies (SB). Methods: This monocentric observational study included a cohort of 277 patients with no prior history of PCa who underwent 3 MRI-TB cores and 14 SB cores with an FSA-TP from January to December 2023. The intraclass correlation coefficient (ICC) was assessed to evaluate the correlation between the Prostate Imaging–Reporting and Data System (PI-RADS) of the index lesion and the International Society of Urological Pathology (ISUP) grade stratified according to prostate zone and region of index lesion at MRI. Multivariate logistic regression analysis was conducted to identify factors associated with PCa and csPCa in patients with discordant results between MRI-TB and SB. Results: FSA-TP-MRI-TB demonstrated higher detection rates of both ciPCa and csPCa in the anterior, apical, and intermediate zones when each of the three MRI-TB cores was analysed separately (p < 0.01). However, when all MRI-TB cores were combined, no significant differences were observed in detection rates across prostate zones (apex, mid, base; p = 0.57) or regions (anterior vs. posterior; p = 0.34). Concordance between radiologic and histopathologic findings, as measured by the intraclass correlation coefficient (ICC), was similar across all zones (apex ICC: 0.33; mid ICC: 0.34; base ICC: 0.38) and regions (anterior ICC: 0.42; posterior ICC: 0.26). Univariate analysis showed that in patients with PCa detected on SB but with negative MRI-TB, older age was the only significant predictor (p = 0.04). Multivariate analysis revealed that patients with PCa detected on MRI-TB but with negative SB, only PSA remained a significant predictor (OR 1.2, 95% CI 1.1–1.4; p = 0.01). In cases with csPCa detected on MRI-TB but with negative SB, age (OR: 1.0, 95% CI 1.0–1.1; p = 0.02), positive digital rectal examination (OR: 2.0, 95% CI 1.1–3.8; p = 0.03), PI-RADS score >3 (OR: 4.5, 95% CI 1.7–12.1; p < 0.01), and larger lesion size (OR: 1.1, 95% CI 1.1–1.2; p < 0.01) were significant predictors. Conclusions: FSA-TP using 14 SB cores and 3 MRI-TB cores ensures comprehensive sampling of all prostate regions, including anterior and apical zones, without significant differences in detection rates between nodules across different zones. Only in a small percentage of patients was csPCa detected exclusively by SB, highlighting the small but important complementary value of combining SB and MRI-TB Full article

(This article belongs to the Special Issue Advances in Prostate Biopsy: From Innovative Imaging Modalities to Optimized Detection Strategies)

9 pages, 1502 KiB

Open AccessOpinion

FAP-Directed Imaging and Therapy in Head and Neck Cancer of Unknown Primary

by Sophie C. Kunte, Gabriel T. Sheikh, Frederik L. Giesel, Martin Canis and Rudolf A. Werner

Cancers 2025, 17(13), 2205; https://doi.org/10.3390/cancers17132205 - 30 Jun 2025

Abstract

Head and neck cancer encompasses a diverse group of malignancies arising from various anatomical subsites, e [...] Full article

(This article belongs to the Special Issue Head and Neck Cancer: Advanced PET/CT and MRI Imaging with a Focus on Current and Emerging Molecular Theranostics)

► Show Figures

Figure 1

14 pages, 3880 KiB

Open AccessArticle

Metastasis-Specific CpG Island DNA Hypermethylation of the Long Non-Coding RNA Gene 00404 in Renal Cell Carcinoma

by Pouriya Faraj Tabrizi, Inga Schimansky, Inga Peters, Jörg Hennenlotter, Hossein Tezval, Markus Antonius Kuczyk and Jürgen Serth

Cancers 2025, 17(13), 2204; https://doi.org/10.3390/cancers17132204 - 30 Jun 2025

Abstract

Background/Objectives: Alterations in long non-protein-coding RNAs (lncRNAs) are known to influence cellular proliferation, apoptosis, and metastasis in human cancers, including renal cell carcinoma (RCC). Methods: Using pyrosequencing, we analyzed DNA methylation (DNAm) at 23 loci within the LINC00404 CpG island across 28 human [...] Read more.

Background/Objectives: Alterations in long non-protein-coding RNAs (lncRNAs) are known to influence cellular proliferation, apoptosis, and metastasis in human cancers, including renal cell carcinoma (RCC). Methods: Using pyrosequencing, we analyzed DNA methylation (DNAm) at 23 loci within the LINC00404 CpG island across 28 human cancer cell line models, 181 RCC tumor tissues, 154 paired tumor-adjacent normal tissues (adNs), and 194 metastatic tissue samples. Results: Our analysis revealed that all CpG sites exhibited tumor-specific hypermethylation (all p ≤ 1.4 × 10⁻⁵). Moreover, primary RCC tissues with distant metastases (M1) and metastatic tissue samples (Mtx) showed significant hypermethylation compared to RCC without distant metastases (M0). Notably, DNAm in Mtx displayed a significant increase in 22 CpG sites, compared to 12 CpG sites in the M1/M0 comparison, suggesting that DNAm in Mtx differs both qualitatively and quantitatively. Conclusions: Given that elevated levels of DNAm were also observed in the majority of cell line models, our findings suggest that LINC00404 may play a pivotal role in the malignant development and progression of RCC metastasis, as well as in other human cancers. Full article

(This article belongs to the Section Cancer Biomarkers)

► Show Figures

Figure 1

19 pages, 11984 KiB

Open AccessArticle

Zinc Finger Protein-Based Prognostic Signature Predicts Survival in Lung Adenocarcinoma

by Lihui Yu, Yahui Zhou and Jingyu Chen

Cancers 2025, 17(13), 2203; https://doi.org/10.3390/cancers17132203 - 30 Jun 2025

Abstract

Background: Zinc finger proteins (ZNFs), functioning as pervasive transcriptional modulators, serve as pivotal mediators of tumorigenesis and malignant advancement. However, the mechanistic contributions of these epigenetic orchestrators to lung adenocarcinoma pathogenesis remain incompletely characterized. Methods: To elucidate zinc finger proteins’ biological [...] Read more.

Background: Zinc finger proteins (ZNFs), functioning as pervasive transcriptional modulators, serve as pivotal mediators of tumorigenesis and malignant advancement. However, the mechanistic contributions of these epigenetic orchestrators to lung adenocarcinoma pathogenesis remain incompletely characterized. Methods: To elucidate zinc finger proteins’ biological significance in lung adenocarcinoma (LUAD) pathogenesis, we first extracted relevant transcriptional data from TCGA. After preliminary screening with univariate Cox regression, a LASSO algorithm was applied to optimize the risk score model, incorporating key zinc finger protein markers. For independent validation, we accessed GEO dataset GSE68465, applying identical analytical protocols to confirm model generalizability. We performed multivariable Cox regression to identify independent predictors of clinical outcomes after adjusting for confounding variables. Cell-based validation included (1) comparative analysis of zinc finger protein expression across LUAD/normal cell models and (2) technical verification using standardized qRT-PCR protocols. Results: Following rigorous bioinformatics screening comprising differential expression and survival analysis, the final 21-zinc finger protein cohort was selected for risk score algorithm development aimed at clinical outcome prediction. Stratification based on computed risk scores revealed markedly superior survival outcomes in the low-risk cohort compared to high-risk patients. Comparative analysis revealed overall concordance in the transcriptional profiles of eight ZNFs (|coef| > 0.1) across experimental cell systems and TCGA datasets. Conclusions: Collectively, the prognostic framework incorporating zinc finger proteins demonstrates biomarker utility in lung adenocarcinoma survival prediction, while offering novel avenues for molecular target discovery in therapeutic strategies against this malignancy. Full article

(This article belongs to the Section Cancer Informatics and Big Data)

► Show Figures

Figure 1

19 pages, 1798 KiB

Open AccessReview

Current Status of Multimodal Therapy for Oligometastatic Disease, Induced Oligometastatic Disease, and Oligo-Progressive Disease in EGFR-Mutated Non-Small-Cell Lung Cancer

by Taichi Miyawaki, Hirotsugu Kenmotsu, Ryo Ko, Masaki Oshima, Takehito Shukuya, Naoto Shikama and Kazuhisa Takahashi

Cancers 2025, 17(13), 2202; https://doi.org/10.3390/cancers17132202 - 30 Jun 2025

Abstract

Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) have shown clinical activity for patients with EGFR-mutated non-small-cell lung cancer (NSCLC). However, the development of resistance to EGFR-TKIs is almost inevitable, posing a significant barrier to long-term survival. Local ablative therapy (LAT) may [...] Read more.

Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) have shown clinical activity for patients with EGFR-mutated non-small-cell lung cancer (NSCLC). However, the development of resistance to EGFR-TKIs is almost inevitable, posing a significant barrier to long-term survival. Local ablative therapy (LAT) may facilitate the prolonged survival of patients with oligometastatic NSCLC. Therapeutic combinations of EGFR-TKIs and LAT for residual disease have been suggested to be potentially effective in EGFR-mutated NSCLC with induced oligometastatic disease, wherein a few lesions remain following initial EGFR-TKI treatment. Various resistance pathways for third-generation EGFR-TKIs including osimertinib, current standard of care for patients with EGFR-mutated NSCLC, have also been identified. In addition to resistance mechanisms, the disease-progression pattern may be an essential element for achieving long-term response and survival. Oligo-progressive disease is a state in which only a few lesions become resistant, whereas many lesions remain controlled with effective systemic therapy. Previous studies have shown that LAT for all oligo-progressive lesions could provide survival benefits. This review discusses the current treatment options and potential future therapeutic developments for patients with EGFR-mutated NSCLC who have synchronous oligometastatic disease, oligo-residual disease during treatment with EGFR-TKIs, and oligo-progressive disease following resistance to EGFR-TKIs. Full article

(This article belongs to the Special Issue The Current Status of Treatment for Oligometastatic Lung Cancer)

► Show Figures

Figure 1

22 pages, 506 KiB

Open AccessReview

Breaking Dogmas in Axillary Lymphadenectomy and Quality of Life

by Sandra López Gordo, Jaime Jimeno-Fraile, Anna García-Monferrer, Pau Nicolau, Neus Ruiz-Edo, Elena Ramirez-Maldonado, Santiago Rojas and Cristina Serra-Serra

Cancers 2025, 17(13), 2201; https://doi.org/10.3390/cancers17132201 - 30 Jun 2025

Abstract

Axillary lymph node dissection (ALND), although increasingly less necessary, is still required in specific breast cancer surgery scenarios, such as cases with a high axillary tumor burden. However, traditional practices are being reassessed due to the associated morbidity and impacts on recovery. This [...] Read more.

Axillary lymph node dissection (ALND), although increasingly less necessary, is still required in specific breast cancer surgery scenarios, such as cases with a high axillary tumor burden. However, traditional practices are being reassessed due to the associated morbidity and impacts on recovery. This review explores five critical and controversial innovations in ALND: (1) same-day discharge, (2) omission of surgical drains, (3) application of fibrin sealants, (4) minimally invasive techniques, and (5) their collective influence on quality of life (QoL). Same-day discharge has proven to be safe and cost-effective, increasing patient satisfaction without raising complication rates. The omission of drains, while slightly increasing seroma volumes, is linked to shorter hospital stays and fewer complications. The use of fibrin sealants shows promising results in reducing the seroma volume and duration, expediting recovery, although their routine use remains under debate. Minimally invasive and endoscopic techniques reduce morbidity and improve cosmetic outcomes while maintaining oncological safety. Quality of life (QoL) is essential in the evaluation of breast cancer treatment and is evaluated using tools such as EORTC QLQ-C30, QLQ-BR23, and FACT-B, SF-36, which assess physical, emotional, and psychosocial recovery. Innovations in ALND seem to improve QoL by minimizing pain, increasing arm function, and reducing psychological stress, underscoring the importance of patient-centered strategies. Although axillary lymphadenectomy increases arm morbidity compared to sentinel node biopsy, its overall impact on quality of life appears limited, likely due to the overlapping effects of systemic therapies and breast surgery. Full article

(This article belongs to the Special Issue New Developments in Breast Cancer Surgery, Risk, and Related Quality of Life)

► Show Figures

Figure 1

16 pages, 638 KiB

Open AccessArticle

De Novo Renal Cell Carcinoma in Kidney Transplant Recipients: Incidence, Outcomes, and Therapeutic Challenges

by Jacob Schmidt, Malte Lehnert, Isabel Lichy, Henning Plage, Jonathan Jeutner, Lukas Kurz, Bernhard Ralla, Markus H. Lerchbaumer, Thorsten Schlomm, Frank Friedersdorff, Andreas Maxeiner and Robert Peters

Cancers 2025, 17(13), 2200; https://doi.org/10.3390/cancers17132200 - 30 Jun 2025

Abstract

Background/Objectives: Kidney transplantation is associated with an increased risk of renal cell carcinoma (RCC). This study aimed to evaluate the outcomes of de novo RCC in kidney transplant recipients (KTRs). Methods: We retrospectively identified 50 de novo RCC cases among 4012 [...] Read more.

Background/Objectives: Kidney transplantation is associated with an increased risk of renal cell carcinoma (RCC). This study aimed to evaluate the outcomes of de novo RCC in kidney transplant recipients (KTRs). Methods: We retrospectively identified 50 de novo RCC cases among 4012 KTRs transplanted from 2005 to 2024. Data on patient characteristics and outcomes were collected. Propensity score matching (PSM) compared 34 localized RCC cases in KTRs with 34 non-transplant RCC cases. The statistical analyses used Kaplan–Meier estimates, the log-rank test, and the Cox regression. Results: The RCC incidence was 0.64 per 1000 person-years, with a standardized incidence ratio of 4.40 (95% CI: 3.33–5.80). In the KTR cohort, clear cell RCC was present in 42%, and papillary RCC was present in 42%. RCC developed predominantly in native kidneys (92%). UICC stage I was present in 74%. The treatment for the non-metastatic RCC was nephrectomy in the majority of cases (91%). For the metastatic RCC, 71% received a tyrosine kinase inhibitor (TKI). In the KTR cohort, the 3- and 5-year overall survival (OS) rates were 85% and 72%, respectively, with a median OS of 199 months; the synchronous metastasized (M1) patients had a median OS of 14 months. Rejection, age, advanced UICC stage, higher pT stage, clinical positive lymph nodes, M1, and higher grade were significantly associated with poor OS. The 5-year OS (96% vs. 84%, p = 0.72) and MFS (92% vs. 93%, p = 0.61) were comparable in the PSM cohort between the KTRs and the non-KTRs in the localized RCC. Conclusions: KTRs have a higher risk of RCC and present at a localized stage with comparable OS rates to non-transplant RCC patients. Adverse tumor characteristics, including synchronous metastases, significantly affect the prognosis, highlighting the need for surveillance and individualized treatment, particularly for metastatic RCC. Full article

(This article belongs to the Special Issue Cancer Risk Factors and Prognosis in Transplant Patients)

► Show Figures

Figure 1

30 pages, 4062 KiB

Open AccessReview

Tumour- and Non-Tumour-Associated Factors That Modulate Response to PD-1/PD-L1 Inhibitors in Non-Small Cell Lung Cancer

by Maryam Khalil and Ming-Sound Tsao

Cancers 2025, 17(13), 2199; https://doi.org/10.3390/cancers17132199 - 30 Jun 2025

Abstract

The interaction of programmed cell death receptor 1 (PD-1) on the surface of immune cells with its ligand, programmed cell death ligand 1 (PD-L1), expressed on tumour cells and antigen-presenting cells, leads to tumour immune evasion. Antibodies that target either PD-1 or its [...] Read more.

The interaction of programmed cell death receptor 1 (PD-1) on the surface of immune cells with its ligand, programmed cell death ligand 1 (PD-L1), expressed on tumour cells and antigen-presenting cells, leads to tumour immune evasion. Antibodies that target either PD-1 or its ligand PD-L1 have shown a favourable response in cancer patients, especially those with non-small cell lung cancer (NSCLC). However, only 15 to 25% of advanced NSCLC patients will benefit from immunotherapy. The PD-L1 tumour proportion score (TPS) is the current standard biomarker to select patients for PD-1/PD-L1 blockade therapy, as patients with a high PD-L1 TPS show better response compared to patients with a low PD-L1 TPS. However, since PD-L1 expression is a continuous variable and is an imperfect biomarker, investigation into additional predictive markers is warranted. This review focuses on tumour- and non-tumour-associated factors that have been shown to affect the response to PD-1/PD-L1 inhibitors in NSCLC. We also delve into mechanistic and clinical evidence on these potential biomarkers and their relationship to the tumour microenvironment (TME). Full article

(This article belongs to the Special Issue Immunotherapy of Non-Small Cell Lung Cancer)

► Show Figures

Figure 1

23 pages, 676 KiB

Open AccessReview

Cardiotoxicity in Elderly Breast Cancer Patients

by Kalliopi Keramida, Anastasia Constantinidou, Dorothea Tsekoura, Effrosyni Kampouroglou, Chrissovalantis Aidarinis, Emmanouil Saloustros, Georgia Karanasiou, Gaia Giulia Angela Sacco, Erika Matos, Andri Papakonstantinou, Manolis Tsiknakis, Cameron Brown, Athos Antoniades, Carlo Cipolla, Daniela Cardinale, Dimitrios Fotiadis, Gerasimos Filippatos and Investigators CARDIOCARE Consortium

Cancers 2025, 17(13), 2198; https://doi.org/10.3390/cancers17132198 - 30 Jun 2025

Abstract

Cardiotoxicity is a leading cause of mortality in the growing populations of elderly breast cancer (BC) patients. Breast cancer treatment in the elderly is highly challenging due to its heterogeneous nature and the lack of specific evidence, as this population is usually underrepresented [...] Read more.

Cardiotoxicity is a leading cause of mortality in the growing populations of elderly breast cancer (BC) patients. Breast cancer treatment in the elderly is highly challenging due to its heterogeneous nature and the lack of specific evidence, as this population is usually underrepresented in randomized clinical trials. Decision making requires a comprehensive approach, considering the type and stage of BC, the patient’s overall health status, life expectancy, geriatric and frailty assessment, the risk of cancer recurrence, comorbidities, cardiotoxicity risk, and the patient’s preferences. The cardiotoxic effects of BC treatments cover the whole spectrum of cardiovascular diseases: heart failure, hypertension, arrhythmias, and myocardial ischemia. Cardiotoxicity risk in these patients is defined by several factors: anticancer therapies, polypharmacy, established cardiovascular disease, comorbidities, frailty, cellular senescence, hormonal changes, and genetic predisposition. Preventive oncological and cardio-oncological strategies, as well as patients’ education, are critical for improved outcomes. Prospective clinical trials in this population are urgently needed. Full article

(This article belongs to the Section Cancer Survivorship and Quality of Life)

► Show Figures

Figure 1

17 pages, 1490 KiB

Open AccessArticle

Mir-16 Decreases the Expression of VTI1B and SMPD1, Genes Involved in Membrane-Protein Trafficking in Melanoma

by Adi Layani, Tal Meningher, Yechezkel Sidi, Dror Avni and Raya Leibowitz

Cancers 2025, 17(13), 2197; https://doi.org/10.3390/cancers17132197 - 29 Jun 2025

Abstract

Introduction: The interface between T cells and the tumor microenvironment, termed the ‘immunological synapse’, consists of multiple checkpoint protein pairs co-expressed on both sides of the synapse. mir-16, a microRNA from a widely known tumor-suppressor family of miRNAs, was previously shown by us [...] Read more.

Introduction: The interface between T cells and the tumor microenvironment, termed the ‘immunological synapse’, consists of multiple checkpoint protein pairs co-expressed on both sides of the synapse. mir-16, a microRNA from a widely known tumor-suppressor family of miRNAs, was previously shown by us to be downregulated in melanoma. As other miRNAs from this family have been shown to directly target checkpoint proteins, here we investigated whether miR-16 influences the expression patterns of checkpoint proteins in melanoma. Methods: Single-cell gene expression data from the melanoma microenvironment were retrieved from a public database. Melanoma cell lines were established from metastatic lesions and transiently transfected with an hsa-miR-16-5p-mimic RNA or a mir-16-expressing plasmid. The mRNA expression profiles were analyzed using an Affymetrix microarray. Direct targets of miR-16 were identified by luciferase reporter assays. Protein levels were assessed by Western blotting. Results: Bioinformatic analysis revealed that the expression levels of eight checkpoint mRNAs, known to be present on the melanoma side of the immunological synapse, were highly correlated. Four of these mRNAs contained putative binding sites for the miR-15/16 family. miR-16 expression was significantly reduced in melanoma cells, compared to normal melanocytes. Luciferase reporter assays demonstrated that miR-16 directly targets the 3′ untranslated regions (3′UTRs) of CD40, CD80. The mRNAs downregulated following miR-16 overexpression were highly enriched for genes involved in autophagy, vesicle-mediated transport, and the regulation of protein membrane localization. Among these, VTI1B and SMPD1 were confirmed to be direct targets of miR-16. Transient overexpression of miR-16 resulted in a significant reduction in SMPD1 and VTI1B levels in melanoma cell lines. Conclusions: Our findings suggest that miR-16 potentially modulates melanoma tumorigenesis, metastasis and immunogenicity by altering the composition of checkpoint proteins at the immunological synapse and by regulating cellular pathways associated with intracellular trafficking and transmembrane protein presentation. Full article

(This article belongs to the Special Issue Exploring Non-Coding RNA Signatures in Cancer: Definitions and Implications for Diagnosis and Therapy)

► Show Figures

Figure 1

32 pages, 1613 KiB

Open AccessReview

Ultra-Processed Diets and Endocrine Disruption, Explanation of Missing Link in Rising Cancer Incidence Among Young Adults

by Almir Fajkić, Orhan Lepara, Rijad Jahić, Almira Hadžović-Džuvo, Andrej Belančić, Alexander Chupin, Doris Pavković and Emina Karahmet Sher

Cancers 2025, 17(13), 2196; https://doi.org/10.3390/cancers17132196 - 29 Jun 2025

Abstract

The global increase in early-onset cancers among adolescents and young adults has happened at the same time as the rise in the consumption of ultra-processed foods (UPFs). Far beyond their poor nutritional quality, UPFs are increasingly seen as Trojan horses, complex biological agents [...] Read more.

The global increase in early-onset cancers among adolescents and young adults has happened at the same time as the rise in the consumption of ultra-processed foods (UPFs). Far beyond their poor nutritional quality, UPFs are increasingly seen as Trojan horses, complex biological agents that interfere with many functions of the human organism. In this review, we utilise the Trojan horse model to explain the quiet and building health risks from UPFs as foods that seem harmless, convenient, and affordable while secretly delivering endocrine-disrupting chemicals (EDCs), causing chronic low-grade inflammation, altering the microbiome, and producing epigenetic alterations. We bring together new proof showing that UPFs mess up hormonal signals, harm the body’s ability to fight off harmful germs, lead to an imbalance of microbes, and cause detrimental changes linked to cancer. Important components, such as bisphenols and phthalates, can migrate from containers into food, while additional ingredients and effects from cooking disrupt the normal balance of cells. These exposures are especially harmful during vulnerable developmental periods and may lay the groundwork for disease many years later. The Trojan horse model illustrates the hidden nature of UPF-related damage, not through a sudden toxin but via chronic dysregulation of metabolic, hormonal, and genetic control. This model changes focus from usual diet worries to a bigger-picture view of UPFs as causes of life-disrupting damage. Ultimately, this review aims to identify gaps in current knowledge and epidemiological approaches and highlight the need for multi-omics, long-term studies and personalised nutrition plans to assess and reduce the cancer risk associated with UPFs. Recognising UPFs as a silent disruptor is crucial in shaping public health policies and cancer prevention programs targeting younger people. Full article

(This article belongs to the Special Issue Lifestyle Choices and Endocrine Dysfunction on Cancer Onset and Risk)

► Show Figures

Figure 1

Journal Description

Cancers

Latest Articles

Journal Menu

Journal Browser

Highly Accessed Articles

Latest Books

E-Mail Alert

News

Topics

Conferences

Special Issues

Topical Collections

Further Information

Guidelines

MDPI Initiatives

Follow MDPI