Journal Description
Cancers
Cancers
is a peer-reviewed, open access journal of oncology, published semimonthly online by MDPI. The Irish Association for Cancer Research (IACR), Spanish Association for Cancer Research (ASEICA), Biomedical Research Centre (CIBM), British Neuro-Oncology Society (BNOS) and Spanish Group for Cancer Immuno-Biotherapy (GÉTICA) are affiliated with Cancers and their members receive a discount on the article processing charges.
- Open Access— free for readers, with article processing charges (APC) paid by authors or their institutions.
- High Visibility: indexed within Scopus, SCIE (Web of Science), PubMed, PMC, Embase, CAPlus / SciFinder, and other databases.
- Journal Rank: JCR - Q2 (Oncology) / CiteScore - Q1 (Oncology)
- Rapid Publication: manuscripts are peer-reviewed and a first decision is provided to authors approximately 17.9 days after submission; acceptance to publication is undertaken in 2.8 days (median values for papers published in this journal in the second half of 2023).
- Recognition of Reviewers: reviewers who provide timely, thorough peer-review reports receive vouchers entitling them to a discount on the APC of their next publication in any MDPI journal, in appreciation of the work done.
- Sections: published in 18 topical sections.
- Companion journals for Cancers include: Radiation and Onco.
Impact Factor:
5.2 (2022);
5-Year Impact Factor:
5.6 (2022)
Latest Articles
Dissecting the Puzzling Roles of FAM46C: A Multifaceted Pan-Cancer Tumour Suppressor with Increasing Clinical Relevance
Cancers 2024, 16(9), 1706; https://doi.org/10.3390/cancers16091706 (registering DOI) - 27 Apr 2024
Abstract
FAM46C is a well-established tumour suppressor with a role that is not completely defined or universally accepted. Although FAM46C expression is down-modulated in several tumours, significant mutations in the FAM46C gene are only found in multiple myeloma (MM). Consequently, its tumour suppressor activity
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FAM46C is a well-established tumour suppressor with a role that is not completely defined or universally accepted. Although FAM46C expression is down-modulated in several tumours, significant mutations in the FAM46C gene are only found in multiple myeloma (MM). Consequently, its tumour suppressor activity has primarily been studied in the MM context. However, emerging evidence suggests that FAM46C is involved also in other cancer types, namely colorectal, prostate and gastric cancer and squamous cell and hepatocellular carcinoma, where FAM46C expression was found to be significantly reduced in tumoural versus non-tumoural tissues and where FAM46C was shown to possess anti-proliferative properties. Accordingly, FAM46C was recently proposed to function as a pan-cancer prognostic marker, bringing FAM46C under the spotlight and attracting growing interest from the scientific community in the pathways modulated by FAM46C and in its mechanistic activity. Here, we will provide the first comprehensive review regarding FAM46C by covering (1) the intracellular pathways regulated by FAM46C, namely the MAPK/ERK, PI3K/AKT, β-catenin and TGF-β/SMAD pathways; (2) the models regarding its mode of action, specifically the poly(A) polymerase, intracellular trafficking modulator and inhibitor of centriole duplication models, focusing on connections and interdependencies; (3) the regulation of FAM46C expression in different environments by interferons, IL-4, TLR engagement or transcriptional modulators; and, lastly, (4) how FAM46C expression levels associate with increased/decreased tumour cell sensitivity to anticancer agents, such as bortezomib, dexamethasone, lenalidomide, pomalidomide, doxorubicin, melphalan, SK1-I, docetaxel and norcantharidin.
Full article
(This article belongs to the Special Issue Unique Perspectives in Cancer Signaling)
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Open AccessReview
Survivin as a Therapeutic Target for the Treatment of Human Cancer
by
Qiang Wang and Mark I. Greene
Cancers 2024, 16(9), 1705; https://doi.org/10.3390/cancers16091705 (registering DOI) - 27 Apr 2024
Abstract
Survivin was initially identified as a member of the inhibitor apoptosis (IAP) protein family and has been shown to play a critical role in the regulation of apoptosis. More recent studies showed that survivin is a component of the chromosome passenger complex and
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Survivin was initially identified as a member of the inhibitor apoptosis (IAP) protein family and has been shown to play a critical role in the regulation of apoptosis. More recent studies showed that survivin is a component of the chromosome passenger complex and acts as an essential mediator of mitotic progression. Other potential functions of survivin, such as mitochondrial function and autophagy, have also been proposed. Survivin has emerged as an attractive target for cancer therapy because its overexpression has been found in most human cancers and is frequently associated with chemotherapy resistance, recurrence, and poor survival rates in cancer patients. In this review, we discuss our current understanding of how survivin mediates various aspects of malignant transformation and drug resistance, as well as the efforts that have been made to develop therapeutics targeting survivin for the treatment of cancer.
Full article
(This article belongs to the Collection Innovations in Cancer Drug Development Research)
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Open AccessReview
Targeting TRPV4 Channels for Cancer Pain Relief
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Caren Tatiane de David Antoniazzi, Náthaly Andrighetto Ruviaro, Diulle Spat Peres, Patrícia Rodrigues, Fernanda Tibolla Viero and Gabriela Trevisan
Cancers 2024, 16(9), 1703; https://doi.org/10.3390/cancers16091703 (registering DOI) - 27 Apr 2024
Abstract
Despite the unique and complex nature of cancer pain, the activation of different ion channels can be related to the initiation and maintenance of pain. The transient receptor potential vanilloid 4 (TRPV4) is a cation channel broadly expressed in sensory afferent neurons. This
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Despite the unique and complex nature of cancer pain, the activation of different ion channels can be related to the initiation and maintenance of pain. The transient receptor potential vanilloid 4 (TRPV4) is a cation channel broadly expressed in sensory afferent neurons. This channel is activated by multiple stimuli to mediate pain perception associated with inflammatory and neuropathic pain. Here, we focused on summarizing the role of TRPV4 in cancer etiology and cancer-induced pain mechanisms. Many studies revealed that the administration of a TRPV4 antagonist and TRPV4 knockdown diminishes nociception in chemotherapy-induced peripheral neuropathy (CIPN). Although the evidence on TRPV4 channels’ involvement in cancer pain is scarce, the expression of these receptors was reportedly enhanced in cancer-induced bone pain (CIBP), perineural, and orofacial cancer models following the inoculation of tumor cells to the bone marrow cavity, sciatic nerve, and tongue, respectively. Effective pain management is a continuous problem for patients diagnosed with cancer, and current guidelines fail to address a mechanism-based treatment. Therefore, examining new molecules with potential antinociceptive properties targeting TRPV4 modulation would be interesting. Identifying such agents could lead to the development of treatment strategies with improved pain-relieving effects and fewer adverse effects than the currently available analgesics.
Full article
(This article belongs to the Special Issue Cancer Pain: From Basic Research to Drug Discovery and Clinical Studies)
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Open AccessReview
Review of Psilocybin Use for Depression among Cancer Patients after Approval in Oregon
by
Val Bellman
Cancers 2024, 16(9), 1702; https://doi.org/10.3390/cancers16091702 (registering DOI) - 27 Apr 2024
Abstract
Despite the legalization of psilocybin therapy for depression in terminal illnesses such as advanced cancer through Oregon’s Measure 109 in 2020, significant challenges have impeded its implementation. This review synthesizes the empirical data supporting the utilization of psilocybin therapy for addressing cancer-related depression,
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Despite the legalization of psilocybin therapy for depression in terminal illnesses such as advanced cancer through Oregon’s Measure 109 in 2020, significant challenges have impeded its implementation. This review synthesizes the empirical data supporting the utilization of psilocybin therapy for addressing cancer-related depression, including an evaluation of its purported benefits and potential adverse effects. It provides a comprehensive examination of therapeutic strategies, dosing regimens, and barriers to ensuring responsible and equitable access. Salient issues explored include the development of ethical protocols, integration within healthcare systems, ensuring statewide availability, resolving legal ambiguities, and defining clinical standards. Oregon’s pioneering role serves as a case study, highlighting the necessity of addressing regulatory, logistical, and ethical obstacles to ensure the establishment of rigorous and equitable psilocybin care models.
Full article
(This article belongs to the Special Issue Updates on Depression among Cancer Patients)
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Open AccessArticle
Socioeconomic Deprivation and Invasive Breast Cancer Incidence by Stage at Diagnosis: A Possible Explanation to the Breast Cancer Social Paradox
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Giulio Borghi, Claire Delacôte, Solenne Delacour-Billon, Stéphanie Ayrault-Piault, Tienhan Sandrine Dabakuyo-Yonli, Patricia Delafosse, Anne-Sophie Woronoff, Brigitte Trétarre, Florence Molinié and Anne Cowppli-Bony
Cancers 2024, 16(9), 1701; https://doi.org/10.3390/cancers16091701 (registering DOI) - 27 Apr 2024
Abstract
In this study, we assessed the influence of area-based socioeconomic deprivation on the incidence of invasive breast cancer (BC) in France, according to stage at diagnosis. All women from six mainland French departments, aged 15+ years, and diagnosed with a primary invasive breast
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In this study, we assessed the influence of area-based socioeconomic deprivation on the incidence of invasive breast cancer (BC) in France, according to stage at diagnosis. All women from six mainland French departments, aged 15+ years, and diagnosed with a primary invasive breast carcinoma between 2008 and 2015 were included (n = 33,298). Area-based socioeconomic deprivation was determined using the French version of the European Deprivation Index. Age-standardized incidence rates (ASIR) by socioeconomic deprivation and stage at diagnosis were compared estimating incidence rate ratios (IRRs) adjusted for age at diagnosis and rurality of residence. Compared to the most affluent areas, significantly lower IRRs were found in the most deprived areas for all-stages (0.85, 95% CI 0.81–0.89), stage I (0.77, 95% CI 0.72–0.82), and stage II (0.84, 95% CI 0.78–0.90). On the contrary, for stages III–IV, significantly higher IRRs (1.18, 95% CI 1.08–1.29) were found in the most deprived areas. These findings provide a possible explanation to similar or higher mortality rates, despite overall lower incidence rates, observed in women living in more deprived areas when compared to their affluent counterparts. Socioeconomic inequalities in access to healthcare services, including screening, could be plausible explanations for this phenomenon, underlying the need for further research.
Full article
(This article belongs to the Special Issue Disparities in Cancer Prevention, Screening, Diagnosis and Management)
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Open AccessArticle
Application of Deep Learning for Real-Time Ablation Zone Measurement in Ultrasound Imaging
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Corinna Zimmermann, Adrian Michelmann, Yannick Daniel, Markus D. Enderle, Nermin Salkic and Walter Linzenbold
Cancers 2024, 16(9), 1700; https://doi.org/10.3390/cancers16091700 (registering DOI) - 27 Apr 2024
Abstract
Background: The accurate delineation of ablation zones (AZs) is crucial for assessing radiofrequency ablation (RFA) therapy’s efficacy. Manual measurement, the current standard, is subject to variability and potential inaccuracies. Aim: This study aims to assess the effectiveness of Artificial Intelligence (AI) in automating
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Background: The accurate delineation of ablation zones (AZs) is crucial for assessing radiofrequency ablation (RFA) therapy’s efficacy. Manual measurement, the current standard, is subject to variability and potential inaccuracies. Aim: This study aims to assess the effectiveness of Artificial Intelligence (AI) in automating AZ measurements in ultrasound images and compare its accuracy with manual measurements in ultrasound images. Methods: An in vitro study was conducted using chicken breast and liver samples subjected to bipolar RFA. Ultrasound images were captured every 15 s, with the AI model Mask2Former trained for AZ segmentation. The measurements were compared across all methods, focusing on short-axis (SA) metrics. Results: We performed 308 RFA procedures, generating 7275 ultrasound images across liver and chicken breast tissues. Manual and AI measurement comparisons for ablation zone diameters revealed no significant differences, with correlation coefficients exceeding 0.96 in both tissues (p < 0.001). Bland–Altman plots and a Deming regression analysis demonstrated a very close alignment between AI predictions and manual measurements, with the average difference between the two methods being −0.259 and −0.243 mm, for bovine liver and chicken breast tissue, respectively. Conclusion: The study validates the Mask2Former model as a promising tool for automating AZ measurement in RFA research, offering a significant step towards reducing manual measurement variability.
Full article
(This article belongs to the Special Issue Endoscopic Ultrasound in Cancer Research)
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Open AccessReview
Rehabilitation in People Living with Glioblastoma: A Narrative Review of the Literature
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Anna Zanotto, Rebecca N. Glover, Tobia Zanotto and Florien W. Boele
Cancers 2024, 16(9), 1699; https://doi.org/10.3390/cancers16091699 (registering DOI) - 27 Apr 2024
Abstract
Glioblastoma is the most common primary malignant brain tumor. While preliminary data point to the positive effects of rehabilitation for patients with glioblastoma, there are unique challenges for clinicians working with this population, including limited life expectancy and/or rapid neurological deterioration. The aim
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Glioblastoma is the most common primary malignant brain tumor. While preliminary data point to the positive effects of rehabilitation for patients with glioblastoma, there are unique challenges for clinicians working with this population, including limited life expectancy and/or rapid neurological deterioration. The aim of this article is to review the literature on rehabilitation of adults with glioblastoma, including the feasibility of interventions, their effectiveness, as well as the current clinical practice. The reviewed literature suggests that rehabilitation has been found beneficial for improving the functional prognosis and quality of life of adults with glioblastoma and is desired by patients. We summarize the qualitative evidence regarding healthcare professionals’ and patients’ perspectives on the use of supportive care services. We conclude there is a need for the design of effective rehabilitation programs for patients with glioblastoma, as well as for the development of glioblastoma-specific clinical guidelines for rehabilitation practitioners.
Full article
(This article belongs to the Special Issue Advances in Survival of Glioblastoma)
Open AccessArticle
Identifying the Trends of Urinary microRNAs within Extracellular Vesicles for Esophageal Cancer
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Kazuhiko Hisaoka, Satoru Matsuda, Kodai Minoura, Hiroki Yamaguchi, Yuki Ichikawa, Mika Mizunuma, Ryota Kobayashi, Yosuke Morimoto, Masashi Takeuchi, Kazumasa Fukuda, Rieko Nakamura, Shutaro Hori, Taigi Yamazaki, Takehiko Sambe, Hirofumi Kawakubo and Yuko Kitagawa
Cancers 2024, 16(9), 1698; https://doi.org/10.3390/cancers16091698 (registering DOI) - 27 Apr 2024
Abstract
Background: The advancement of multidisciplinary treatment has increased the need to develop tests to monitor tumor burden during treatment. We herein analyzed urinary microRNAs within extracellular vesicles from patients with esophageal squamous cell carcinoma (ESCC) and normal individuals using a microarray. Methods:
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Background: The advancement of multidisciplinary treatment has increased the need to develop tests to monitor tumor burden during treatment. We herein analyzed urinary microRNAs within extracellular vesicles from patients with esophageal squamous cell carcinoma (ESCC) and normal individuals using a microarray. Methods: Patients with advanced ESCC who underwent esophagectomy (A), endoscopic submucosal resection (ESD) (B), and healthy donors (C) were included. Based on microRNA expression among the groups (Analysis 1), microRNAs with significant differences between groups A and C were selected (Analysis 2). Of these candidates, microRNAs in which the change between A and C was consistent with the change between B and C were selected for downstream analysis (Analysis 3). Finally, microRNA expression was validated in patients with recurrence from A (exploratory analysis). Results: For analysis 1, 205 microRNAs were selected. For Analyses 2 and 3, the changes in 18 microRNAs were consistent with changes in tumor burden as determined by clinical imaging and pathological findings. The AUC for the detection of ESCC using 18 microRNAs was 0.72. In exploratory analysis, three of eighteen microRNAs exhibited a concordant trend with recurrence. Conclusions: The current study identified the urinary microRNAs which were significantly expressed in ESCC patients. Validation study is warranted to evaluate whether these microRNAs could reflect tumor burden during multidisciplinary treatment for ESCC.
Full article
(This article belongs to the Special Issue Preoperative Chemoradiotherapy for Gastrointestinal Cancer)
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Open AccessReview
A Review of the Paradigmatic Role of Adipose Tissue in Renal Cancer: Fat Measurement and Tumor Behavior Features
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Eliodoro Faiella, Elva Vergantino, Federica Vaccarino, Amalia Bruno, Gloria Perillo, Rosario Francesco Grasso, Bruno Beomonte Zobel and Domiziana Santucci
Cancers 2024, 16(9), 1697; https://doi.org/10.3390/cancers16091697 (registering DOI) - 27 Apr 2024
Abstract
(1) Background: Renal-cell carcinoma (RCC) incidence has been steadily rising, with obesity identified as a potential risk factor. However, the relationship between obesity and RCC prognosis remains unclear. This systematic review aims to investigate the impact of different adipose tissue measurements on RCC
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(1) Background: Renal-cell carcinoma (RCC) incidence has been steadily rising, with obesity identified as a potential risk factor. However, the relationship between obesity and RCC prognosis remains unclear. This systematic review aims to investigate the impact of different adipose tissue measurements on RCC behavior and prognosis. (2) Methods: A search of MEDLINE databases identified 20 eligible studies focusing on various fat measurements, including visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), perirenal adipose tissue (PRAT), and the Mayo adhesive probability (MAP) score. (3) Results: The review revealed conflicting findings regarding the association between adipose tissue measurements and RCC outcomes. While some studies suggested a protective role of certain fat deposits, particularly VAT, against disease progression and mortality, others reported contradictory results across different adipose metrics and RCC subtypes. (4) Conclusions: Methodological variations and limitations, such as retrospective designs and sample size constraints, pose challenges to standardization and generalizability. Further research is needed to understand these associations better and establish standardized approaches for adiposity assessment in RCC patients, which could inform clinical practice and therapeutic decision-making.
Full article
(This article belongs to the Special Issue Cell Biology of Cancer Invasion)
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Open AccessReview
Updates in Cancer Cachexia: Clinical Management and Pharmacologic Interventions
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Sudeep Pandey, Lauren Bradley and Egidio Del Fabbro
Cancers 2024, 16(9), 1696; https://doi.org/10.3390/cancers16091696 (registering DOI) - 27 Apr 2024
Abstract
Despite a better understanding of the mechanisms causing cancer cachexia (CC) and development of promising pharmacologic and supportive care interventions, CC persists as an underdiagnosed and undertreated condition. CC contributes to fatigue, poor quality of life, functional impairment, increases treatment related toxicity, and
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Despite a better understanding of the mechanisms causing cancer cachexia (CC) and development of promising pharmacologic and supportive care interventions, CC persists as an underdiagnosed and undertreated condition. CC contributes to fatigue, poor quality of life, functional impairment, increases treatment related toxicity, and reduces survival. The core elements of CC such as weight loss and poor appetite should be identified early. Currently, addressing contributing conditions (hypothyroidism, hypogonadism, and adrenal insufficiency), managing nutrition impact symptoms leading to decreased oral intake (nausea, constipation, dysgeusia, stomatitis, mucositis, pain, fatigue, depressed mood, or anxiety), and the addition of pharmacologic agents when appropriate (progesterone analog, corticosteroids, and olanzapine) is recommended. In Japan, the clinical practice has changed based on the availability of Anamorelin, a ghrelin receptor agonist that improved lean body mass, weight, and appetite-related quality of life (QoL) compared to a placebo, in phase III trials. Other promising therapeutic agents currently in trials include Espindolol, a non-selective β blocker and a monoclonal antibody to GDF-15. In the future, a single therapeutic agent or perhaps multiple medications targeting the various mechanisms of CC may prove to be an effective strategy. Ideally, these medications should be incorporated into a multimodal interdisciplinary approach that includes exercise and nutrition.
Full article
(This article belongs to the Special Issue Advances in Supportive and Palliative Care in Cancer)
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Open AccessArticle
Synergistic Action of Benzyl Isothiocyanate and Sorafenib in a Nanoparticle Delivery System for Enhanced Triple-Negative Breast Cancer Treatment
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Qi Wang, Nan Cheng, Wei Wang and Yongping Bao
Cancers 2024, 16(9), 1695; https://doi.org/10.3390/cancers16091695 - 26 Apr 2024
Abstract
Triple-negative breast cancer (TNBC) presents a therapeutic challenge due to its complex pathology and limited treatment options. Addressing this challenge, our study focuses on the effectiveness of combination therapy, which has recently become a critical strategy in cancer treatment, improving therapeutic outcomes and
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Triple-negative breast cancer (TNBC) presents a therapeutic challenge due to its complex pathology and limited treatment options. Addressing this challenge, our study focuses on the effectiveness of combination therapy, which has recently become a critical strategy in cancer treatment, improving therapeutic outcomes and combating drug resistance and metastasis. We explored a novel combination therapy employing Benzyl isothiocyanate (BITC) and Sorafenib (SOR) and their nanoformulation, aiming to enhance therapeutic outcomes against TNBC. Through a series of in vitro assays, we assessed the cytotoxic effects of BITC and SOR, both free and encapsulated. The BITC–SOR-loaded nanoparticles (NPs) were synthesized using an amphiphilic copolymer, which demonstrated a uniform spherical morphology and favorable size distribution. The encapsulation efficiencies, as well as the sustained release profiles at varied pH levels, were quantified, revealing distinct kinetics that were well-modeled by the Korsmeyer–Peppas equation. The NP delivery system showed a marked dose-dependent cytotoxicity towards TNBC cells, with an IC50 of 7.8 μM for MDA-MB-231 cells, indicating improved efficacy over free drugs, while exhibiting minimal toxicity toward normal breast cells. Furthermore, the NPs significantly inhibited cell migration and invasion in TNBC models, surpassing the effects of free drugs. These findings underscore the potential of BITC–SOR-NPs as a promising therapeutic approach for TNBC, offering targeted delivery while minimizing systemic toxicity.
Full article
(This article belongs to the Special Issue Triple Negative Breast Cancer Therapy Resistance and Metastasis)
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Open AccessReview
Proton Therapy in Non-Rhabdomyosarcoma Soft Tissue Sarcomas of Children and Adolescents
by
Sabina Vennarini, Francesca Colombo, Alfredo Mirandola, Ester Orlandi, Emilia Pecori, Stefano Chiaravalli, Maura Massimino, Michela Casanova and Andrea Ferrari
Cancers 2024, 16(9), 1694; https://doi.org/10.3390/cancers16091694 - 26 Apr 2024
Abstract
This paper provides insights into the use of Proton Beam Therapy (PBT) in pediatric patients with non-rhabdomyosarcoma soft tissue sarcomas (NRSTS). NRSTS are a heterogeneous group of rare and aggressive mesenchymal extraskeletal tumors, presenting complex and challenging clinical management scenarios. The overall survival
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This paper provides insights into the use of Proton Beam Therapy (PBT) in pediatric patients with non-rhabdomyosarcoma soft tissue sarcomas (NRSTS). NRSTS are a heterogeneous group of rare and aggressive mesenchymal extraskeletal tumors, presenting complex and challenging clinical management scenarios. The overall survival rate for patients with NRSTS is around 70%, but the outcome is strictly related to the presence of various variables, such as the histological subtype, grade of malignancy and tumor stage at diagnosis. Multimodal therapy is typically considered the preferred treatment for high-grade NRSTS. Radiotherapy plays a key role in the treatment of children and adolescents with NRSTS. However, the potential for radiation-induced side effects partially limits its use. Therefore, PBT represents a very suitable therapeutic option for these patients. The unique depth-dose characteristics of protons can be leveraged to minimize doses to healthy tissue significantly, potentially allowing for increased tumor doses and enhanced preservation of surrounding tissues. These benefits suggest that PBT may improve local control while reducing toxicity and improving quality of life. While clear evidence of therapeutic superiority of PBT over other modern photon techniques in NRSTS is still lacking—partly due to the limited data available—PBT can be an excellent treatment option for young patients with these tumors. A dedicated international comprehensive collaborative approach is essential to better define its role within the multidisciplinary management of NRSTS. Shared guidelines for PBT indications—based on the patient’s age, estimated outcome, and tumor location—and centralization in high-level referral centers are needed to optimize the use of resources, since access to PBT remains a challenge due to the limited number of available proton therapy facilities.
Full article
(This article belongs to the Section Pediatric Oncology)
Open AccessArticle
Genomic Characterization of Partial Tandem Duplication Involving the KMT2A Gene in Adult Acute Myeloid Leukemia
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Andrew Seto, Gregory Downs, Olivia King, Shabnam Salehi-Rad, Ana Baptista, Kayu Chin, Sylvie Grenier, Bevoline Nwachukwu, Anne Tierens, Mark D. Minden, Adam C. Smith and José-Mario Capo-Chichi
Cancers 2024, 16(9), 1693; https://doi.org/10.3390/cancers16091693 - 26 Apr 2024
Abstract
Background: Gene rearrangements affecting KMT2A are frequent in acute myeloid leukemia (AML) and are often associated with a poor prognosis. KMT2A gene fusions are often detected by chromosome banding analysis and confirmed by fluorescence in situ hybridization. However, small intragenic insertions, termed KMT2A
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Background: Gene rearrangements affecting KMT2A are frequent in acute myeloid leukemia (AML) and are often associated with a poor prognosis. KMT2A gene fusions are often detected by chromosome banding analysis and confirmed by fluorescence in situ hybridization. However, small intragenic insertions, termed KMT2A partial tandem duplication (KMT2A-PTD), are particularly challenging to detect using standard molecular and cytogenetic approaches. Methods: We have validated the use of a custom hybrid-capture-based next-generation sequencing (NGS) panel for comprehensive profiling of AML patients seen at our institution. This NGS panel targets the entire consensus coding DNA sequence of KMT2A. To deduce the presence of a KMT2A-PTD, we used the relative ratio of KMT2A exons coverage. We sought to corroborate the KMT2A-PTD NGS results using (1) multiplex-ligation probe amplification (MLPA) and (2) optical genome mapping (OGM). Results: We analyzed 932 AML cases and identified 41 individuals harboring a KMT2A-PTD. MLPA, NGS, and OGM confirmed the presence of a KMT2A-PTD in 22 of the cases analyzed where orthogonal testing was possible. The two false-positive KMT2A-PTD calls by NGS could be explained by the presence of cryptic structural variants impacting KMT2A and interfering with KMT2A-PTD analysis. OGM revealed the nature of these previously undetected gene rearrangements in KMT2A, while MLPA yielded inconclusive results. MLPA analysis for KMT2A-PTD is limited to exon 4, whereas NGS and OGM resolved KMT2A-PTD sizes and copy number levels. Conclusions: KMT2A-PTDs are complex gene rearrangements that cannot be fully ascertained using a single genomic platform. MLPA, NGS panels, and OGM are complementary technologies applied in standard-of-care testing for AML patients. MLPA and NGS panels are designed for targeted copy number analysis; however, our results showed that integration of concurrent genomic alterations is needed for accurate KMT2A-PTD identification. Unbalanced chromosomal rearrangements overlapping with KMT2A can interfere with the diagnostic sensitivity and specificity of copy-number-based KMT2A-PTD detection methodologies.
Full article
(This article belongs to the Special Issue Optical Genome Mapping in Hematological Malignancies)
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Open AccessSystematic Review
The Association between Blood Test Trends and Undiagnosed Cancer: A Systematic Review and Critical Appraisal
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Pradeep S. Virdee, Kiana K. Collins, Claire Friedemann Smith, Xin Yang, Sufen Zhu, Sophie E. Roberts, Nia Roberts, Jason L. Oke, Clare Bankhead, Rafael Perera, FD Richard Hobbs and Brian D. Nicholson
Cancers 2024, 16(9), 1692; https://doi.org/10.3390/cancers16091692 - 26 Apr 2024
Abstract
Clinical guidelines include monitoring blood test abnormalities to identify patients at increased risk of undiagnosed cancer. Noting blood test changes over time may improve cancer risk stratification by considering a patient’s individual baseline and important changes within the normal range. We aimed to
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Clinical guidelines include monitoring blood test abnormalities to identify patients at increased risk of undiagnosed cancer. Noting blood test changes over time may improve cancer risk stratification by considering a patient’s individual baseline and important changes within the normal range. We aimed to review the published literature to understand the association between blood test trends and undiagnosed cancer. MEDLINE and EMBASE were searched until 15 May 2023 for studies assessing the association between blood test trends and undiagnosed cancer. We used descriptive summaries and narratively synthesised studies. We included 29 articles. Common blood tests were haemoglobin (24%, n = 7), C-reactive protein (17%, n = 5), and fasting blood glucose (17%, n = 5), and common cancers were pancreatic (29%, n = 8) and colorectal (17%, n = 5). Of the 30 blood tests studied, an increasing trend in eight (27%) was associated with eight cancer types, and a decreasing trend in 17 (57%) with 10 cancer types. No association was reported between trends in 11 (37%) tests and breast, bile duct, glioma, haematological combined, liver, prostate, or thyroid cancers. Our review highlights trends in blood tests that could facilitate the identification of individuals at increased risk of undiagnosed cancer. For most possible combinations of tests and cancers, there was limited or no evidence.
Full article
(This article belongs to the Section Systematic Review or Meta-Analysis in Cancer Research)
Open AccessReview
Update in the Treatment of Pleural Tumors: Robotic Surgery Combined with Hyperthermic Intrathoracic Chemotherapy
by
Gaetano Romano, Carmelina Cristina Zirafa, Ilaria Ceccarelli, Gianmarco Elia, Federico Davini and Franca Melfi
Cancers 2024, 16(9), 1691; https://doi.org/10.3390/cancers16091691 - 26 Apr 2024
Abstract
(1) Background. Intracavitary hyperthermic chemotherapy (HITHOC) remains part of the complex mosaic that is the multimodal approach for advanced stage thymoma and pleural malignancies. However, robotic pleurectomy/removal of pleural lesions in combination with intrathoracic chemotherapy is not currently being investigated. The aim of
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(1) Background. Intracavitary hyperthermic chemotherapy (HITHOC) remains part of the complex mosaic that is the multimodal approach for advanced stage thymoma and pleural malignancies. However, robotic pleurectomy/removal of pleural lesions in combination with intrathoracic chemotherapy is not currently being investigated. The aim of this study is to evaluate the safety of robotic pleurectomy/removal of relapses and HITHOC in patients with pleural recurrence of thymoma or MPM. (2) Methods: The data of nine consecutive patients affected by thymoma relapses or MPM who underwent robotic surgery in combination with HITHOC from February 2017 to November 2022 were collected and analyzed. Surgery performed prior to intrathoracic infusion of high-temperature chemotherapy consisted of removal of recurrences (three patients) or pleurectomy (six patients). All surgeries were performed with a four-port, fully robotic technique. (3) Results: No intraoperative complications occurred. No renal complications related to infusion were recorded. One patient, who underwent pleurectomy for MPM, had a grade II Clavien–Dindo postoperative complication. Oncological follow-up showed results in line with the literature. (4) Conclusion: With the limitation of the small number of patients, robotic surgery in combination with HITHOC seems to be safe in patients with pleural relapses of thymoma and early-stage MPM.
Full article
(This article belongs to the Section Cancer Biomarkers)
Open AccessReview
Current and Future Therapeutic Targets for Directed Molecular Therapies in Cholangiocarcinoma
by
Philipp Heumann, Andreas Albert, Karsten Gülow, Denis Tümen, Martina Müller and Arne Kandulski
Cancers 2024, 16(9), 1690; https://doi.org/10.3390/cancers16091690 - 26 Apr 2024
Abstract
We conducted a comprehensive review of the current literature of published data, clinical trials (MEDLINE; ncbi.pubmed.com), congress contributions (asco.org; esmo.org), and active recruiting clinical trains (clinicaltrial.gov) on targeted therapies in cholangiocarcinoma. Palliative treatment regimens were analyzed as well as preoperative and perioperative treatment
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We conducted a comprehensive review of the current literature of published data, clinical trials (MEDLINE; ncbi.pubmed.com), congress contributions (asco.org; esmo.org), and active recruiting clinical trains (clinicaltrial.gov) on targeted therapies in cholangiocarcinoma. Palliative treatment regimens were analyzed as well as preoperative and perioperative treatment options. We summarized the current knowledge for each mutation and molecular pathway that is or has been under clinical evaluation and discussed the results on the background of current treatment guidelines. We established and recommended targeted treatment options that already exist for second-line settings, including IDH-, BRAF-, and NTRK-mutated tumors, as well as for FGFR2 fusion, HER2/neu-overexpression, and microsatellite instable tumors. Other options for targeted treatment include EGFR- or VEGF-dependent pathways, which are known to be overexpressed or dysregulated in this cancer type and are currently under clinical investigation. Targeted therapy in CCA is a hallmark of individualized medicine as these therapies aim to specifically block pathways that promote cancer cell growth and survival, leading to tumor shrinkage and improved patient outcomes based on the molecular profile of the tumor.
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(This article belongs to the Special Issue New Insights into the Management of Intrahepatic Cholangiocarcinoma)
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Open AccessArticle
A Simple Frailty Score Predicts Survival and Early Mortality in Systemic AL Amyloidosis
by
Rafael Ríos-Tamayo, Ramón Lecumberri, María Teresa Cibeira, Verónica González-Calle, Rafael Alonso, Amalia Domingo-González, Elena Landete, Cristina Encinas, Belén Iñigo, María-Jesús Blanchard, Elena Alejo, Isabel Krsnik, Manuel Gómez-Bueno, Pablo Garcia-Pavia, Javier Segovia-Cubero, Laura Rosiñol, Juan-José Lahuerta, Joaquín Martínez-López and Joan Bladé
Cancers 2024, 16(9), 1689; https://doi.org/10.3390/cancers16091689 - 26 Apr 2024
Abstract
Systemic AL amyloidosis is a challenging disease for which many patients are considered frail in daily clinical practice. However, no study has so far addressed frailty and its impact on the outcome of these patients. We built a simple score to predict mortality
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Systemic AL amyloidosis is a challenging disease for which many patients are considered frail in daily clinical practice. However, no study has so far addressed frailty and its impact on the outcome of these patients. We built a simple score to predict mortality based on three frailty-associated variables: age, ECOG performance status (<2 vs. ≥2) and NT-proBNP (<8500 vs. ≥8500 ng/L). Four-hundred and sixteen consecutive newly diagnosed patients diagnosed at ten sites from the Spanish Myeloma Group were eligible for the study. The score was developed in a derivation cohort from a referral center, and it was externally validated in a multicenter cohort. Multivariate analysis showed that the three variables were independent predictors of survival. The score was able to discriminate four groups of patients in terms of overall survival and early mortality in both cohorts. Comorbidity was also analyzed with the Charlson comorbidity index, but it did not reach statistical significance in the model. A nomogram was created to easily estimate the mortality risk of each patient at each time point. This score is a simple, robust, and efficient approach to dynamically assess frailty-dependent mortality both at diagnosis and throughout follow-up. The optimal treatment for frail AL amyloidosis patients remains to be determined but we suggest that the estimation of frailty-associated risk could complement current staging systems, adding value in clinical decision-making in this complex scenario.
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(This article belongs to the Section Clinical Research of Cancer)
Open AccessArticle
Association of miR-146a-5p and miR-21-5p with Prognostic Features in Melanomas
by
Maria Naddeo, Elisabetta Broseghini, Federico Venturi, Sabina Vaccari, Barbara Corti, Martina Lambertini, Costantino Ricci, Beatrice Fontana, Giorgio Durante, Milena Pariali, Biagio Scotti, Giulia Milani, Elena Campione, Manuela Ferracin and Emy Dika
Cancers 2024, 16(9), 1688; https://doi.org/10.3390/cancers16091688 - 26 Apr 2024
Abstract
Background: Cutaneous melanoma (CM) is one of the most lethal tumors among skin cancers and its incidence is rising worldwide. Recent data support the role of microRNAs (miRNAs) in melanoma carcinogenesis and their potential use as disease biomarkers. Methods: We quantified the expression
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Background: Cutaneous melanoma (CM) is one of the most lethal tumors among skin cancers and its incidence is rising worldwide. Recent data support the role of microRNAs (miRNAs) in melanoma carcinogenesis and their potential use as disease biomarkers. Methods: We quantified the expression of miR-146a-5p and miR-21-5p in 170 formalin-fixed paraffin embedded (FFPE) samples of CM, namely 116 superficial spreading melanoma (SSM), 26 nodular melanoma (NM), and 28 lentigo maligna melanoma (LMM). We correlated miRNA expression with specific histopathologic features including Breslow thickness (BT), histological subtype, ulceration and regression status, and mitotic index. Results: miR-146a-5p and miR-21-5p were significantly higher in NM compared to SSM and LMM. The positive correlation between miR-146a-5p and miR-21-5p expression and BT was confirmed for both miRNAs in SSM. Considering the ulceration status, we assessed that individual miR-21-5p expression was significantly higher in ulcerated CMs. The increased combined expression of the two miRNAs was strongly associated with ulceration (p = 0.0093) and higher mitotic rate (≥1/mm2) (p = 0.0005). We demonstrated that the combination of two-miRNA expression and prognostic features (BT and ulceration) can better differentiate cutaneous melanoma prognostic groups, considering overall survival and time-to-relapse clinical outcomes. Specifically, miRNA expression can further stratify prognostic groups among patients with BT ≥ 0.8 mm but without ulceration. Our findings provide further insights into the characterization of CM with specific prognostic features. The graphical abstract was created with BioRender.com.
Full article
(This article belongs to the Special Issue Melanoma: Clinical Trials and Translational Research)
Open AccessArticle
Development of an Artificial-Intelligence-Based Tool for Automated Assessment of Cellularity in Bone Marrow Biopsies in Ph-Negative Myeloproliferative Neoplasms
by
Giuseppe D’Abbronzo, Antonio D’Antonio, Annarosaria De Chiara, Luigi Panico, Lucianna Sparano, Anna Diluvio, Antonello Sica, Gino Svanera, Renato Franco and Andrea Ronchi
Cancers 2024, 16(9), 1687; https://doi.org/10.3390/cancers16091687 - 26 Apr 2024
Abstract
The cellularity assessment in bone marrow biopsies (BMBs) for the diagnosis of Philadelphia chromosome (Ph)-negative myeloproliferative neoplasms (MPNs) is a key diagnostic feature and is usually performed by the human eyes through an optical microscope with consequent inter-observer and intra-observer variability. Thus, the
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The cellularity assessment in bone marrow biopsies (BMBs) for the diagnosis of Philadelphia chromosome (Ph)-negative myeloproliferative neoplasms (MPNs) is a key diagnostic feature and is usually performed by the human eyes through an optical microscope with consequent inter-observer and intra-observer variability. Thus, the use of an automated tool may reduce variability, improving the uniformity of the evaluation. The aim of this work is to develop an accurate AI-based tool for the automated quantification of cellularity in BMB histology. A total of 55 BMB histological slides, diagnosed as Ph- MPN between January 2018 and June 2023 from the archives of the Pathology Unit of University “Luigi Vanvitelli” in Naples (Italy), were scanned on Ventana DP200 or Epredia P1000 and exported as whole-slide images (WSIs). Fifteen BMBs were randomly selected to obtain a training set of AI-based tools. An expert pathologist and a trained resident performed annotations of hematopoietic tissue and adipose tissue, and annotations were exported as .tiff images and .png labels with two colors (black for hematopoietic tissue and yellow for adipose tissue). Subsequently, we developed a semantic segmentation model for hematopoietic tissue and adipose tissue. The remaining 40 BMBs were used for model verification. The performance of our model was compared with an evaluation of the cellularity of five expert hematopathologists and three trainees; we obtained an optimal concordance between our model and the expert pathologists’ evaluation, with poorer concordance for trainees. There were no significant differences in cellularity assessments between two different scanners.
Full article
(This article belongs to the Special Issue Quantitative Imaging and Digital Pathology in Clinical Cancer Research)
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Digital Pathology for Better Clinical Practice
by
Assia Hijazi, Carlo Bifulco, Pamela Baldin and Jérôme Galon
Cancers 2024, 16(9), 1686; https://doi.org/10.3390/cancers16091686 - 26 Apr 2024
Abstract
(1) Background: Digital pathology (DP) is transforming the landscape of clinical practice, offering a revolutionary approach to traditional pathology analysis and diagnosis. (2) Methods: This innovative technology involves the digitization of traditional glass slides which enables pathologists to access, analyze, and share high-resolution
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(1) Background: Digital pathology (DP) is transforming the landscape of clinical practice, offering a revolutionary approach to traditional pathology analysis and diagnosis. (2) Methods: This innovative technology involves the digitization of traditional glass slides which enables pathologists to access, analyze, and share high-resolution whole-slide images (WSI) of tissue specimens in a digital format. By integrating cutting-edge imaging technology with advanced software, DP promises to enhance clinical practice in numerous ways. DP not only improves quality assurance and standardization but also allows remote collaboration among experts for a more accurate diagnosis. Artificial intelligence (AI) in pathology significantly improves cancer diagnosis, classification, and prognosis by automating various tasks. It also enhances the spatial analysis of tumor microenvironment (TME) and enables the discovery of new biomarkers, advancing their translation for therapeutic applications. (3) Results: The AI-driven immune assays, Immunoscore (IS) and Immunoscore-Immune Checkpoint (IS-IC), have emerged as powerful tools for improving cancer diagnosis, prognosis, and treatment selection by assessing the tumor immune contexture in cancer patients. Digital IS quantitative assessment performed on hematoxylin–eosin (H&E) and CD3+/CD8+ stained slides from colon cancer patients has proven to be more reproducible, concordant, and reliable than expert pathologists’ evaluation of immune response. Outperforming traditional staging systems, IS demonstrated robust potential to enhance treatment efficiency in clinical practice, ultimately advancing cancer patient care. Certainly, addressing the challenges DP has encountered is essential to ensure its successful integration into clinical guidelines and its implementation into clinical use. (4) Conclusion: The ongoing progress in DP holds the potential to revolutionize pathology practices, emphasizing the need to incorporate powerful AI technologies, including IS, into clinical settings to enhance personalized cancer therapy.
Full article
(This article belongs to the Special Issue Predictive Biomarkers for Colorectal Cancer)
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