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
The Effects of National Insurance Coverage Expansion and Genetic Counseling’s Role on BRCA1/2 Mutation Tests in Breast Cancer Patients
Cancers 2024, 16(10), 1865; https://doi.org/10.3390/cancers16101865 (registering DOI) - 14 May 2024
Abstract
Purpose: This study aims to evaluate the impact of South Korea’s national insurance coverage (NIC) expansion and the addition of genetic counselors on BRCA1/2 mutation testing rates in breast cancer patients. Materials and Methods: A retrospective review was conducted at the Samsung Medical
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Purpose: This study aims to evaluate the impact of South Korea’s national insurance coverage (NIC) expansion and the addition of genetic counselors on BRCA1/2 mutation testing rates in breast cancer patients. Materials and Methods: A retrospective review was conducted at the Samsung Medical Center (SMC), dividing patients into three groups: pre-NIC expansion, post-NIC expansion, and post-extra genetic counselor involvement. The number of BRCA1/2 tests performed and the detection rates among newly diagnosed and follow-up patients, particularly focusing on triple-negative breast cancer (TNBC) cases, were analyzed. Results: Post-NIC expansion, there was a significant increase in BRCA1/2 testing rates, with a gradual rise in detection rates while maintaining statistical significance. TNBC patients under 60 experienced substantial increases in testing rates. The number of follow-up patients recalled for testing also rose significantly after the extra genetic counselor involvement. Additionally, NIC expansion increased insurance coverage for TNBC patients, enhancing accessibility to testing. Conclusion: The study highlights the positive impact of NIC expansion and genetic counselor involvement on BRCA1/2 mutation testing rates and subsequent patient management. Addressing financial barriers to testing and incorporating genetic counseling significantly improve patient outcomes. This model provides a potential strategy for enhancing early detection and personalized treatment for breast cancer patients with BRCA1/2 mutations, contributing to global cancer management efforts.
Full article
(This article belongs to the Section Cancer Causes, Screening and Diagnosis)
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Open AccessArticle
Identification of Gene Expression in Different Stages of Breast Cancer with Machine Learning
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Ali Abidalkareem, Ali K. Ibrahim, Moaed Abd, Oneeb Rehman and Hanqi Zhuang
Cancers 2024, 16(10), 1864; https://doi.org/10.3390/cancers16101864 (registering DOI) - 14 May 2024
Abstract
Determining the tumor origin in humans is vital in clinical applications of molecular diagnostics. Metastatic cancer is usually a very aggressive disease with limited diagnostic procedures, despite the fact that many protocols have been evaluated for their effectiveness in prognostication. Research has shown
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Determining the tumor origin in humans is vital in clinical applications of molecular diagnostics. Metastatic cancer is usually a very aggressive disease with limited diagnostic procedures, despite the fact that many protocols have been evaluated for their effectiveness in prognostication. Research has shown that dysregulation in miRNAs (a class of non-coding, regulatory RNAs) is remarkably involved in oncogenic conditions. This research paper aims to develop a machine learning model that processes an array of miRNAs in 1097 metastatic tissue samples from patients who suffered from various stages of breast cancer. The suggested machine learning model is fed with miRNA quantitative read count data taken from The Cancer Genome Atlas Data Repository. Two main feature-selection techniques have been used, mainly Neighborhood Component Analysis and Minimum Redundancy Maximum Relevance, to identify the most discriminant and relevant miRNAs for their up-regulated and down-regulated states. These miRNAs are then validated as biological identifiers for each of the four cancer stages in breast tumors. Both machine learning algorithms yield performance scores that are significantly higher than the traditional fold-change approach, particularly in earlier stages of cancer, with Neighborhood Component Analysis and Minimum Redundancy Maximum Relevance achieving accuracy scores of up to 0.983 and 0.931, respectively, compared to 0.920 for the FC method. This study underscores the potential of advanced feature-selection methods in enhancing the accuracy of cancer stage identification, paving the way for improved diagnostic and therapeutic strategies in oncology.
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(This article belongs to the Special Issue Biomarkers in Breast Cancer: Recent Advances and Challenges)
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Open AccessReview
The Neuroblastoma Microenvironment, Heterogeneity and Immunotherapeutic Approaches
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Panagiotis Alkinoos Polychronopoulos, Oscar C. Bedoya-Reina and John Inge Johnsen
Cancers 2024, 16(10), 1863; https://doi.org/10.3390/cancers16101863 - 13 May 2024
Abstract
Neuroblastoma is a peripheral nervous system tumor that almost exclusively occurs in young children. Although intensified treatment modalities have led to increased patient survival, the prognosis for patients with high-risk disease is still around 50%, signifying neuroblastoma as a leading cause of cancer-related
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Neuroblastoma is a peripheral nervous system tumor that almost exclusively occurs in young children. Although intensified treatment modalities have led to increased patient survival, the prognosis for patients with high-risk disease is still around 50%, signifying neuroblastoma as a leading cause of cancer-related deaths in children. Neuroblastoma is an embryonal tumor and is shaped by its origin from cells within the neural crest. Hence, neuroblastoma usually presents with a low mutational burden and is, in the majority of cases, driven by epigenetically deregulated transcription networks. The recent development of Omic techniques has given us detailed knowledge of neuroblastoma evolution, heterogeneity, and plasticity, as well as intra- and intercellular molecular communication networks within the neuroblastoma microenvironment. Here, we discuss the potential of these recent discoveries with emphasis on new treatment modalities, including immunotherapies which hold promise for better future treatment regimens.
Full article
(This article belongs to the Special Issue Neuroblastoma: Molecular Insights and Clinical Implications)
Open AccessReview
Novel Endocrine Therapeutic Opportunities for Estrogen Receptor-Positive Ovarian Cancer—What Can We Learn from Breast Cancer?
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Tine Ottenbourgs and Els Van Nieuwenhuysen
Cancers 2024, 16(10), 1862; https://doi.org/10.3390/cancers16101862 - 13 May 2024
Abstract
Low-grade serous ovarian cancer (LGSOC) is a rare ovarian malignancy primarily affecting younger women and is characterized by an indolent growth pattern. It exhibits indolent growth and high estrogen/progesterone receptor expression, suggesting potential responsiveness to endocrine therapy. However, treatment efficacy remains limited due
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Low-grade serous ovarian cancer (LGSOC) is a rare ovarian malignancy primarily affecting younger women and is characterized by an indolent growth pattern. It exhibits indolent growth and high estrogen/progesterone receptor expression, suggesting potential responsiveness to endocrine therapy. However, treatment efficacy remains limited due to the development of endocrine resistance. The mechanisms of resistance, whether primary or acquired, are still largely unknown and present a significant hurdle in achieving favorable treatment outcomes with endocrine therapy in these patients. In estrogen receptor-positive breast cancer, mechanisms of endocrine resistance have been largely explored and novel treatment strategies to overcome resistance have emerged. Considering the shared estrogen receptor positivity in LGSOC and breast cancer, we wanted to explore whether there are any parallel mechanisms of resistance and whether we can extend endocrine breast cancer treatments to LGSOC. This review aims to highlight the underlying molecular mechanisms possibly driving endocrine resistance in ovarian cancer, while also exploring the available therapeutic opportunities to overcome this resistance. By unraveling the potential pathways involved and examining emerging strategies, this review explores valuable insights for advancing treatment options and improving patient outcomes in LGSOC, which has limited therapeutic options available.
Full article
(This article belongs to the Special Issue Rare Gynecological Cancers)
Open AccessArticle
Molecular Characterization and Therapeutic Opportunities in KRAS Wildtype Pancreatic Ductal Adenocarcinoma
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Aakash Desai, Alexander H. Xiao, Daheui Choi, Merih D. Toruner, Daniel Walden, Thorvardur R. Halfdanarson, Steven Alberts, Robert R. McWilliams, Amit Mahipal, Daniel Ahn, Hani Babiker, Gulnaz Stybayeva, Alexander Revzin, Sani Kizilbash, Alex Adjei, Tanios Bekaii-Saab, Aaron S. Mansfield, Ryan M. Carr and Wen Wee Ma
Cancers 2024, 16(10), 1861; https://doi.org/10.3390/cancers16101861 - 13 May 2024
Abstract
Purpose: To investigate the molecular characteristics of and potential for precision medicine in KRAS wildtype pancreatic ductal adenocarcinoma (PDAC). Patients and Methods: We investigated 27 patients with KRASWT PDAC at our institution. Clinical data were obtained via chart review. Tumor specimens for
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Purpose: To investigate the molecular characteristics of and potential for precision medicine in KRAS wildtype pancreatic ductal adenocarcinoma (PDAC). Patients and Methods: We investigated 27 patients with KRASWT PDAC at our institution. Clinical data were obtained via chart review. Tumor specimens for each subject were interrogated for somatic single nucleotide variants, insertion and deletions, and copy number variants by DNA sequencing. Gene fusions were detected from RNA-seq. A patient-derived organoid (PDO) was developed from a patient with a MET translocation and expanded ex vivo to predict therapeutic sensitivity prior to enrollment in a phase 2 clinical trial. Results: Transcriptomic analysis showed our cohort may be stratified by the relative gene expression of the KRAS signaling cascade. The PDO derived from our patient harboring a TFG-MET rearrangement was found to have in vitro sensitivity to the multi-tyrosine kinase inhibitor crizotinib. The patient was enrolled in the phase 2 SPARTA clinical trial and received monotherapy with vebrelitinib, a c-MET inhibitor, and achieved a partial and durable response. Conclusions: KRASWT PDAC is molecularly distinct from KRASMUT and enriched with potentially actionable genetic variants. In our study, transcriptomic profiling revealed that the KRAS signaling cascade may play a key role in KRASWT PDAC. Our report of a KRASWT PDAC patient with TFG-MET rearrangement who responded to a cMET inhibitor further supports the pursuit of precision oncology in this sub-population. Identification of targetable mutations, perhaps through approaches like RNA-seq, can help enable precision-driven approaches to select optimal treatment based on tumor characteristics.
Full article
(This article belongs to the Collection Oncology: State-of-the-Art Research in the USA)
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Open AccessSystematic Review
Surgical Treatment for Endometrial Cancer, Hysterectomy Performed via Minimally Invasive Routes Compared with Open Surgery: A Systematic Review and Network Meta-Analysis
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Purushothaman Natarajan, Gayathri Delanerolle, Lucy Dobson, Cong Xu, Yutian Zeng, Xuan Yu, Kathleen Marston, Thuan Phan, Fiona Choi, Vanya Barzilova, Simon G. Powell, James Wyatt, Sian Taylor, Jian Qing Shi and Dharani K. Hapangama
Cancers 2024, 16(10), 1860; https://doi.org/10.3390/cancers16101860 - 13 May 2024
Abstract
Background: Total hysterectomy with bilateral salpingo-oophorectomy via minimally invasive surgery (MIS) has emerged as the standard of care for early-stage endometrial cancer (EC). Prior systematic reviews and meta-analyses have focused on outcomes reported solely from randomised controlled trials (RCTs), overlooking valuable data
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Background: Total hysterectomy with bilateral salpingo-oophorectomy via minimally invasive surgery (MIS) has emerged as the standard of care for early-stage endometrial cancer (EC). Prior systematic reviews and meta-analyses have focused on outcomes reported solely from randomised controlled trials (RCTs), overlooking valuable data from non-randomised studies. This inaugural systematic review and network meta-analysis comprehensively compares clinical and oncological outcomes between MIS and open surgery for early-stage EC, incorporating evidence from randomised and non-randomised studies. Methods: This study was prospectively registered on PROSPERO (CRD42020186959). All original research of any experimental design reporting clinical and oncological outcomes of surgical treatment for endometrial cancer was included. Study selection was restricted to English-language peer-reviewed journal articles published 1 January 1995–31 December 2021. A Bayesian network meta-analysis was conducted. Results: A total of 99 studies were included in the network meta-analysis, comprising 181,716 women and 14 outcomes. Compared with open surgery, laparoscopic and robotic-assisted surgery demonstrated reduced blood loss and length of hospital stay but increased operating time. Compared with laparoscopic surgery, robotic-assisted surgery was associated with a significant reduction in ileus (OR = 0.40, 95% CrI: 0.17–0.87) and total intra-operative complications (OR = 0.38, 95% CrI: 0.17–0.75) as well as a higher disease-free survival (OR = 2.45, 95% CrI: 1.04–6.34). Conclusions: For treating early endometrial cancer, minimal-access surgery via robotic-assisted or laparoscopic techniques appears safer and more efficacious than open surgery. Robotic-assisted surgery is associated with fewer complications and favourable oncological outcomes.
Full article
(This article belongs to the Special Issue Surgical Innovations in Gynecologic Oncology: Endometrial and Ovarian Cancer)
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Open AccessReview
The Transformative Role of 3D Culture Models in Triple-Negative Breast Cancer Research
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Xavier S. Bittman-Soto, Evelyn S. Thomas, Madeline E. Ganshert, Laura L. Mendez-Santacruz and J. Chuck Harrell
Cancers 2024, 16(10), 1859; https://doi.org/10.3390/cancers16101859 - 13 May 2024
Abstract
Advancements in cell culturing techniques have allowed the development of three-dimensional (3D) cell culture models sourced directly from patients’ tissues and tumors, faithfully replicating the native tissue environment. These models provide a more clinically relevant platform for studying disease progression and treatment responses
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Advancements in cell culturing techniques have allowed the development of three-dimensional (3D) cell culture models sourced directly from patients’ tissues and tumors, faithfully replicating the native tissue environment. These models provide a more clinically relevant platform for studying disease progression and treatment responses compared to traditional two-dimensional (2D) models. Patient-derived organoids (PDOs) and patient-derived xenograft organoids (PDXOs) emerge as innovative 3D cancer models capable of accurately mimicking the tumor’s unique features, enhancing our understanding of tumor complexities, and predicting clinical outcomes. Triple-negative breast cancer (TNBC) poses significant clinical challenges due to its aggressive nature, propensity for early metastasis, and limited treatment options. TNBC PDOs and PDXOs have significantly contributed to the comprehension of TNBC, providing novel insights into its underlying mechanism and identifying potential therapeutic targets. This review explores the transformative role of various 3D cancer models in elucidating TNBC pathogenesis and guiding novel therapeutic strategies. It also provides an overview of diverse 3D cell culture models, derived from cell lines and tumors, highlighting their advantages and culturing challenges. Finally, it delves into live-cell imaging techniques, endpoint assays, and alternative cell culture media and methodologies, such as scaffold-free and scaffold-based systems, essential for advancing 3D cancer model research and development.
Full article
(This article belongs to the Special Issue Advances in Triple-Negative Breast Cancer)
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Open AccessReview
Oncofertility as an Essential Part of Comprehensive Cancer Treatment in Patients of Reproductive Age, Adolescents and Children
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Dominika Łubik-Lejawka, Iwona Gabriel, Adrianna Marzec and Anita Olejek
Cancers 2024, 16(10), 1858; https://doi.org/10.3390/cancers16101858 - 13 May 2024
Abstract
The number of children, adolescents and young adults diagnosed with cancer has been rising recently. Various oncological treatments have a detrimental effect on female fertility, and childbearing becomes a major issue during surveillance after recovery. This review discusses the impact of oncological treatments
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The number of children, adolescents and young adults diagnosed with cancer has been rising recently. Various oncological treatments have a detrimental effect on female fertility, and childbearing becomes a major issue during surveillance after recovery. This review discusses the impact of oncological treatments on the ovarian reserve with a thorough explanation of oncologic treatments’ effects and modes of oncofertility procedures. The aim of this review is to help clinicians in making an informed decision about post-treatment fertility in their patients. Ultimately, it may lead to improved overall long-term outcomes among young populations suffering from cancer.
Full article
(This article belongs to the Special Issue Gynecologic Cancers: Clinical Research Progress of Resection)
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Open AccessArticle
What Is a Sarcoma ‘Specialist Center’? Multidisciplinary Research Finds an Answer
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Roger Wilson, Denise Reinke, Gerard van Oortmerssen, Ornella Gonzato, Gabriele Ott, Chandrajit P. Raut, B. Ashleigh Guadagnolo, Rick L. M. Haas, Jonathan Trent, Robin Jones, Lauren Pretorius, Brandi Felser, Mandy Basson, Kathrin Schuster and Bernd Kasper
Cancers 2024, 16(10), 1857; https://doi.org/10.3390/cancers16101857 - 13 May 2024
Abstract
The management of sarcomas in specialist centers delivers significant benefits. In much of the world, specialists are not available, and the development of expertise is identified as a major need. However, the terms ‘specialist’ or ‘expert’ center are rarely defined. Our objective is
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The management of sarcomas in specialist centers delivers significant benefits. In much of the world, specialists are not available, and the development of expertise is identified as a major need. However, the terms ‘specialist’ or ‘expert’ center are rarely defined. Our objective is to offer a definition for patient advocates and a tool for healthcare providers to underpin improving the care of people with sarcoma. SPAGN developed a discussion paper for a workshop at the SPAGN 2023 Conference, attended by 75 delegates. A presentation to the Connective Tissue Oncology Society (CTOS) and further discussion led to this paper. Core Principles were identified that underlie specialist sarcoma care. The primary Principle is the multi-disciplinary team discussing every patient, at first diagnosis and during treatment. Principles for optimal sarcoma management include accurate diagnosis followed by safe, high-quality treatment, with curative intent. These Principles are supplemented by Features describing areas of healthcare, professional involvement, and service provision and identifying further research and development needs. These allow for variations because of national or local policies and budgets. We propose the term ‘Sarcoma Intelligent Specialist Network’ to recognize expertise wherever it is found in the world. This provides a base for further discussion and local refinement.
Full article
(This article belongs to the Special Issue Quality and Clinical Outcomes Improvement in the Management of Oncology Patients)
Open AccessReview
Diagnostic Biomarkers in Renal Cell Tumors According to the Latest WHO Classification: A Focus on Selected New Entities
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Francesca Sanguedolce, Roberta Mazzucchelli, Ugo Giovanni Falagario, Angelo Cormio, Magda Zanelli, Andrea Palicelli, Maurizio Zizzo, Albino Eccher, Matteo Brunelli, Andrea Benedetto Galosi, Giuseppe Carrieri and Luigi Cormio
Cancers 2024, 16(10), 1856; https://doi.org/10.3390/cancers16101856 - 13 May 2024
Abstract
The fifth edition of the World Health Organization (WHO) classification for urogenital tumors, released in 2022, introduces some novelties in the chapter on renal epithelial tumors compared to the previous 2016 classification. Significant changes include the recognition of new disease entities and adjustments
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The fifth edition of the World Health Organization (WHO) classification for urogenital tumors, released in 2022, introduces some novelties in the chapter on renal epithelial tumors compared to the previous 2016 classification. Significant changes include the recognition of new disease entities and adjustments in the nomenclature for certain pathologies. Notably, each tumor entity now includes minimum essential and desirable criteria for reliable diagnosis. This classification highlights the importance of biological and molecular characterization alongside traditional cytological and architectural features. In this view, immunophenotyping through immunohistochemistry (IHC) plays a crucial role in bridging morphology and genetics. This article aims to present and discuss the role of key immunohistochemical markers that support the diagnosis of new entities recognized in the WHO classification, focusing on critical topics associated with single markers, in the context of specific tumors, such as the clear cell capillary renal cell tumor (CCPRCT), eosinophilic solid and cystic renal cell carcinoma (ESC-RCC), and so-called “other oncocytic tumors”, namely the eosinophilic vacuolated tumor (EVT) and low-grade oncocytic tumor (LOT). Their distinctive characteristics and immunophenotypic profiles, along with insights regarding diagnostic challenges and the differential diagnosis of these tumors, are provided. This state-of-the-art review offers valuable insights in biomarkers associated with novel renal tumors, as well as a tool to implement diagnostic strategies in routine practice.
Full article
(This article belongs to the Special Issue New Insights into Urologic Oncology)
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Open AccessArticle
Characterization of FOLH1 Expression in Renal Cell Carcinoma
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Eric Ovruchesky, Elizabeth Pan, Melis Guer, Andrew Elliott, Shankar Siva, Praful Ravi, Bradley McGregor, Aditya Bagrodia, Ithaar Derweesh, Pedro Barata, Elisabeth I. Heath, Emmanuel S. Antonarakis, Sourat Darabi, Dave S. B. Hoon, Amir Mortazavi, Toni K. Choueiri, Chadi Nabhan, Shuanzeng Wei and Rana R. McKay
Cancers 2024, 16(10), 1855; https://doi.org/10.3390/cancers16101855 - 13 May 2024
Abstract
Purpose: Given the emergence of PSMA-targeted diagnostic agents and therapeutics, we sought to investigate patterns of FOLH1 expression in RCC and their impacts on RCC outcomes. Methods: We conducted a pooled multi-institutional analysis of patients with RCC having undergone DNA and RNA next-generation
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Purpose: Given the emergence of PSMA-targeted diagnostic agents and therapeutics, we sought to investigate patterns of FOLH1 expression in RCC and their impacts on RCC outcomes. Methods: We conducted a pooled multi-institutional analysis of patients with RCC having undergone DNA and RNA next-generation sequencing. FOLH1-high/low expression was defined as the ≥75th/<25th percentile of RNA transcripts per million (TPM). Angiogenic, T-effector, and myeloid expression signatures were calculated using previously defined gene sets. Kaplan–Meier estimates were calculated from the time of tissue collection or therapy start. Results: We included 1,724 patients in the analysis. FOLH1 expression was significantly higher in clear cell (71%) compared to non-clear cell RCC tumors (19.0 versus 3.3 TPM, p < 0.001) and varied by specimen site (45% primary kidney/55% metastasis, 13.6 versus 9.9 TPM, p < 0.001). FOLH1 expression was correlated with angiogenic gene expression (Spearman = 0.76, p < 0.001) and endothelial cell abundance (Spearman = 0.76, p < 0.001). While OS was similar in patients with FOLH1-high versus -low ccRCC, patients with FOLH1-high clear cell tumors experienced a longer time on cabozantinib treatment (9.7 versus 4.6 months, respectively, HR 0.57, 95% CI 0.35–0.93, p < 0.05). Conclusions: We observed differential patterns of FOLH1 expression based on histology and tumor site in RCC. FOLH1 was correlated with angiogenic gene expression, increased OS, and a longer duration of cabozantinib treatment.
Full article
(This article belongs to the Special Issue Renal Cell Carcinoma: From Pathology to Therapeutic Strategies)
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Open AccessArticle
Daratumumab during Myeloma Induction Therapy Is Associated with Impaired Stem Cell Mobilization and Prolonged Post-Transplant Hematologic Recovery
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Julian Mehl, Dilara Akhoundova, Ulrike Bacher, Barbara Jeker, Gaëlle Rhyner Agocs, Axel Ruefer, Susanne Soltermann, Martin Soekler, Annette Winkler, Michael Daskalakis and Thomas Pabst
Cancers 2024, 16(10), 1854; https://doi.org/10.3390/cancers16101854 - 13 May 2024
Abstract
Daratumumab is being increasingly integrated into first-line multiple myeloma (MM) induction regimens, leading to improved response depth and longer progression-free survival. Autologous stem cell transplantation (ASCT) is commonly performed as a consolidation strategy following first-line induction in fit MM patients. We investigated a
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Daratumumab is being increasingly integrated into first-line multiple myeloma (MM) induction regimens, leading to improved response depth and longer progression-free survival. Autologous stem cell transplantation (ASCT) is commonly performed as a consolidation strategy following first-line induction in fit MM patients. We investigated a cohort of 155 MM patients who received ASCT after first-line induction with or without daratumumab (RVd, n = 110; D-RVd, n = 45), analyzing differences in stem cell mobilization, apheresis, and engraftment. In the D-RVd group, fewer patients successfully completed mobilization at the planned apheresis date (44% vs. 71%, p = 0.0029), and more patients required the use of rescue plerixafor (38% vs. 28%, p = 0.3052). The median count of peripheral CD34+ cells at apheresis was lower (41.37 vs. 52.19 × 106/L, p = 0.0233), and the total number of collected CD34+ cells was inferior (8.27 vs. 10.22 × 106/kg BW, p = 0.0139). The time to recovery of neutrophils and platelets was prolonged (12 vs. 11 days, p = 0.0164; and 16 vs. 14 days, p = 0.0002, respectively), and a higher frequency of erythrocyte transfusions (74% vs. 51%, p = 0.0103) and a higher number of platelet concentrates/patients were required (4 vs. 2; p = 0.001). The use of daratumumab during MM induction might negatively impact stem cell mobilization and engraftment in the context of ASCT.
Full article
(This article belongs to the Special Issue Multiple Myeloma: Recent Advances in Diagnosis, Analysis and Therapeutic Management)
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Open AccessArticle
The Role of T-Cadherin (CDH13) in Treatment Options with Garcinol in Melanoma
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Sebastian Staebler, Sebastian Hoechst, Aranya Thongmao, Nadja Schneider, Anja-Katrin Bosserhoff and Silke Kuphal
Cancers 2024, 16(10), 1853; https://doi.org/10.3390/cancers16101853 - 12 May 2024
Abstract
Targeted therapies with chemotherapeutic agents and immunotherapy with checkpoint inhibitors are among the systemic therapies recommended in the guidelines for clinicians to treat melanoma. Although there have been constant improvements in the treatment of melanoma, resistance to the established therapies continues to occur.
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Targeted therapies with chemotherapeutic agents and immunotherapy with checkpoint inhibitors are among the systemic therapies recommended in the guidelines for clinicians to treat melanoma. Although there have been constant improvements in the treatment of melanoma, resistance to the established therapies continues to occur. Therefore, the purpose of this study was to explore the function of garcinol with regards to specific cancer properties such as proliferation and apoptosis. Garcinol, a natural compound isolated from the plant also known as mangosteen (Garcinia mangostana), is a newly discovered option for cancer treatment. Numerous pharmaceutical substances are derived from plants. For example, the derivates of camptothecin, extracted from the bark of the Chinese tree of happiness (Camptotheca acuminate), or paclitaxel, extracted from the bark of the Western yew tree (Taxus brevifolia), are used as anti-cancer drugs. Here, we show that garcinol reduced proliferation and induced apoptosis in melanoma cell lines. In addition, we found that those cells that are positive for the expression of the cell–cell adhesion molecule T-cadherin (CDH13) respond more sensitively to treatment with garcinol. After knock-down experiments with an siRNA pool against T-cadherin, the sensitivity to garcinol decreased and proliferation and anti-apoptotic behavior of the cells was restored. We conclude that patients who are T-cadherin-positive could especially benefit from a therapy with garcinol.
Full article
(This article belongs to the Special Issue Melanoma: Pathology and Translational Research)
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Open AccessReview
Immunotherapy as a Complement to Surgical Management of Hepatocellular Carcinoma
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Susan J. Kim, Kaelyn C. Cummins and Allan Tsung
Cancers 2024, 16(10), 1852; https://doi.org/10.3390/cancers16101852 - 12 May 2024
Abstract
Hepatocellular carcinoma (HCC) is the most common primary liver tumor in adults, and the fourth leading cause of cancer-related deaths worldwide. While surgical and ablative therapies remain the standard of care in early localized disease, late presentation with advanced stages of disease, impaired
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Hepatocellular carcinoma (HCC) is the most common primary liver tumor in adults, and the fourth leading cause of cancer-related deaths worldwide. While surgical and ablative therapies remain the standard of care in early localized disease, late presentation with advanced stages of disease, impaired hepatic function, or local recurrence following surgical resection preclude operative management as the sole treatment modality in a subgroup of patients. As such, systemic therapies, namely immunotherapy, have become an integral part of the HCC treatment algorithm over the past decade. While agents, such as atezolizumab/bevacizumab, have well-established roles as first-line systemic therapy in intermediate- and advanced-stage HCC, the role of immunotherapy in disease amenable to surgical management continues to evolve. In this review, we will discuss the current evidence and aggregate impact of immunotherapy in the context of HCC amenable to surgical management, including its application in the neoadjuvant and adjuvant settings.
Full article
(This article belongs to the Special Issue Molecular Markers and Targeted Therapy for Hepatobiliary Tumors)
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Open AccessArticle
Unplanned Resections of Soft Tissue Sarcomas—Necessity of Re-Resection?
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Julian Fromm, Alexander Klein, Franziska Mentrup, Lars H. Lindner, Silke Nachbichler, Boris Michael Holzapfel, Sophia Samira Goller, Thomas Knösel and Hans Roland Dürr
Cancers 2024, 16(10), 1851; https://doi.org/10.3390/cancers16101851 - 12 May 2024
Abstract
Background: In soft tissue sarcomas, unplanned resections, or so-called Whoops procedures, do occur quite frequently, thus primarily owing to the abundant presence of benign lesions. Whether re-resection reduces local recurrence or improves overall survival remains a topic of ongoing debate. The principle
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Background: In soft tissue sarcomas, unplanned resections, or so-called Whoops procedures, do occur quite frequently, thus primarily owing to the abundant presence of benign lesions. Whether re-resection reduces local recurrence or improves overall survival remains a topic of ongoing debate. The principle objective of this study was to analyze the outcomes of patients with soft tissue sarcomas of the extremities or trunk wall after an incidental marginal resection by comparing re-resections to individuals who declined the procedure. Methods: A total of 185 patients who underwent unplanned resection were included. These patients were stratified into two groups: Group A (n = 156) underwent re-excision, while Group B (n = 29) was treated conservatively. Depending on the clinical scenario, radio- or chemotherapy was either administered in a neoadjuvant or an adjuvant setting. The presence of residual tumor and metastatic disease was documented. Clinical outcomes, specifically local recurrence (LR), local recurrence-free survival (LRFS) and overall survival (OS), were utilized for evaluation. Results: Group B exhibited significantly larger tumors (p < 0.0001) and a higher mean age than Group A. Among the patients in Group A, 11 (5.9%) had contaminated resection margins (R1), and residual disease (RD) was observed in 93 (59.6%) of the resected specimens. In group B, 10 patients received adjuvant radiotherapy alone, 5 received chemotherapy alone, and 13 underwent a combined approach consisting of both radio- and chemotherapy. In Group A, 8% (n = 12) of the patients developed local recurrence (LR) during the observation period. Conversely, in Group B, this amount was 14% (n = 4) (n.s.). Of the 12 LR in Group A, 10 were found in the subgroup with residual disease. Overall survival and local recurrence-free survival were not significantly different between the groups. A total of 15% (n = 24) of the patients in Group A developed metastatic disease, while 10% (n = 3) in Group B developed metastatic disease (n.s.). Conclusions: Following the reresection of unplanned resected STS, there was no statistically significant difference observed in overall survival or LR compared to patients who did not undergo re-resection. However, within the subgroup of patients with residual disease in the re-resected specimen, the OS was compromised, and the LR rate was higher. Particularly for low-grade lesions, adopting a more conservative approach seems to be justified.
Full article
(This article belongs to the Special Issue Clinical and Surgical Outcomes in the Management of Extremity Soft Tissue Sarcomas)
Open AccessArticle
Targeting Anterior Commissure Involvement with Hyperfractionated Radiotherapy for T1–T2 Squamous Cell Carcinoma of the Glottic Larynx
by
Satoshi Seno, Kazuma Iwashita, Akifumi Kajiwara, Rie Sasaki, Tatsuya Furukawa, Masanori Teshima, Hirotaka Shinomiya, Naomi Kiyota, Rod Lynch, Kenji Yoshida, Takeaki Ishihara, Daisuke Miyawaki, Ken-ichi Nibu and Ryohei Sasaki
Cancers 2024, 16(10), 1850; https://doi.org/10.3390/cancers16101850 - 12 May 2024
Abstract
Anterior commissure is involved in about 20% of early-stage glottic squamous cell carcinomas (EGSCCs). Treatment outcomes and prognostic factors for EGSCC with anterior commissure involvement (ACI) were evaluated by focusing on hyperfractionated radiotherapy (74.4 Gy in 62 fractions). One-hundred and fifty-three patients with
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Anterior commissure is involved in about 20% of early-stage glottic squamous cell carcinomas (EGSCCs). Treatment outcomes and prognostic factors for EGSCC with anterior commissure involvement (ACI) were evaluated by focusing on hyperfractionated radiotherapy (74.4 Gy in 62 fractions). One-hundred and fifty-three patients with T1–T2 EGSCC were included in this study. The median total doses for T1a, T1b, and T2 were 66, 74.4, and 74.4 Gy, respectively. Overall, 49 (32%) patients had T1a, 38 (25%) had T1b, and 66 (43%) had T2 disease. The median treatment duration was 46 days. The median follow-up duration was 5.1 years. The 10-year overall and cause-specific survival rates were 72% and 97%, respectively. The 10-year local control rates were 94% for T1a, 88% for T1b, and 81% for T2 disease. Local control rates in patients with ACI were slightly better than those in patients without ACI with T1a and T1b diseases; however, the difference was not significant. The 10-year laryngeal preservation rate was 96%. Six patients experienced grade 3 mucositis, and four patients had grade 3 dermatitis. Hyperfractionated radiotherapy was effective for T1 disease with ACI, but insufficient for T2 disease with ACI. Our treatment strategy resulted in excellent laryngeal preservation.
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(This article belongs to the Special Issue Clinical and Translational Research in Head and Neck Cancer)
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Surgical Resection in Colorectal Liver Metastasis: An Umbrella Review
by
Martina Milazzo, Letizia Todeschini, Miriam Caimano, Amelia Mattia, Luca Cristin, Alessandro Martinino, Giuseppe Bianco, Gabriele Spoletini and Francesco Giovinazzo
Cancers 2024, 16(10), 1849; https://doi.org/10.3390/cancers16101849 - 12 May 2024
Abstract
Surgical resection is the gold standard for treating synchronous colorectal liver metastases (CRLM). The resection of the primary tumor and metastatic lesions can follow different sequences: “simultaneous”, “bowel-first”, and “liver-first”. Conservative approaches, such as parenchymal-sparing surgery and segmentectomy, may serve as alternatives to
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Surgical resection is the gold standard for treating synchronous colorectal liver metastases (CRLM). The resection of the primary tumor and metastatic lesions can follow different sequences: “simultaneous”, “bowel-first”, and “liver-first”. Conservative approaches, such as parenchymal-sparing surgery and segmentectomy, may serve as alternatives to major hepatectomy. A comprehensive search of Medline, Epistemonikos, Scopus, and the Cochrane Library was conducted. Studies evaluating patients who underwent surgery for CRLM and reported survival results were included. Other secondary outcomes were analyzed, including disease-free survival, perioperative complications and mortality, and recurrence rates. Quality assessment was performed using the AMSTAR-2 method. No significant differences in overall survival, disease-free survival, and secondary outcomes were observed when comparing simultaneous to “bowel-first” resections, despite a higher rate of perioperative mortality in the former group. The 5-year OS was significantly higher for simultaneous resection compared to “liver-first” resection. No significant differences in OS and DFS were noted when comparing “liver-first” to “bowel-first” resection, or anatomic to non-anatomic resection. Our umbrella review validates simultaneous surgery as an effective oncological approach for treating SCRLM, though the increased risk of perioperative morbidity highlights the importance of selecting suitable patients. Non-anatomic resections might be favored to preserve liver function and enable future surgical interventions.
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(This article belongs to the Section Cancer Metastasis)
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Range of Resection in Endometrial Cancer—Clinical Issues of Made-to-Measure Surgery
by
Agnieszka Horala, Sebastian Szubert and Ewa Nowak-Markwitz
Cancers 2024, 16(10), 1848; https://doi.org/10.3390/cancers16101848 - 11 May 2024
Abstract
Endometrial cancer (EC) poses a significant health issue among women, and its incidence has been rising for a couple of decades. Surgery remains its principal treatment method and may have a curative, staging, or palliative aim. The type and extent of surgery depends
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Endometrial cancer (EC) poses a significant health issue among women, and its incidence has been rising for a couple of decades. Surgery remains its principal treatment method and may have a curative, staging, or palliative aim. The type and extent of surgery depends on many factors, and the risks and benefits should be carefully weighed. While simple hysterectomy might be sufficient in early stage EC, modified-radical hysterectomy is sometimes indicated. In advanced disease, the evidence suggests that, similarly to ovarian cancer, optimal cytoreduction improves survival rate. The role of lymphadenectomy in EC patients has long been a controversial issue. The rationale for systematic lymphadenectomy and the procedure of the sentinel lymph node biopsy are thoroughly discussed. Finally, the impact of the molecular classification and new International Federation of Gynecology and Obstetrics (FIGO) staging system on EC treatment is outlined. Due to the increasing knowledge on the pathology and molecular features of EC, as well as the new advances in the adjuvant therapies, the surgical management of EC has become more complex. In the modern approach, it is essential to adjust the extent of the surgery to a specific patient, ensuring an optimal, made-to-measure personalized surgery. This narrative review focuses on the intricacies of surgical management of EC and aims at summarizing the available literature on the subject, providing an up-to-date clinical guide.
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(This article belongs to the Special Issue Gynecologic Cancers: Clinical Research Progress of Resection)
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Targets in the Tumour Matrisome to Promote Cancer Therapy Response
by
Siti Munira Abd Jalil, Jack C. Henry and Angus J. M. Cameron
Cancers 2024, 16(10), 1847; https://doi.org/10.3390/cancers16101847 - 11 May 2024
Abstract
The extracellular matrix (ECM) is composed of complex fibrillar proteins, proteoglycans, and macromolecules, generated by stromal, immune, and cancer cells. The components and organisation of the matrix evolves as tumours progress to invasive disease and metastasis. In many solid tumours, dense fibrotic ECM
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The extracellular matrix (ECM) is composed of complex fibrillar proteins, proteoglycans, and macromolecules, generated by stromal, immune, and cancer cells. The components and organisation of the matrix evolves as tumours progress to invasive disease and metastasis. In many solid tumours, dense fibrotic ECM has been hypothesised to impede therapy response by limiting drug and immune cell access. Interventions to target individual components of the ECM, collectively termed the matrisome, have, however, revealed complex tumour-suppressor, tumour-promoter, and immune-modulatory functions, which have complicated clinical translation. The degree to which distinct components of the matrisome can dictate tumour phenotypes and response to therapy is the subject of intense study. A primary aim is to identify therapeutic opportunities within the matrisome, which might support a better response to existing therapies. Many matrix signatures have been developed which can predict prognosis, immune cell content, and immunotherapy responses. In this review, we will examine key components of the matrisome which have been associated with advanced tumours and therapy resistance. We have primarily focussed here on targeting matrisome components, rather than specific cell types, although several examples are described where cells of origin can dramatically affect tumour roles for matrix components. As we unravel the complex biochemical, biophysical, and intracellular transduction mechanisms associated with the ECM, numerous therapeutic opportunities will be identified to modify tumour progression and therapy response.
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(This article belongs to the Collection The Development of Anti-cancer Agents)
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Current Preoperative Management of Vulvar Squamous Cell Carcinoma: An Overview
by
Luigi Della Corte, Valeria Cafasso, Maria Chiara Guarino, Giuseppe Gullo, Gaspare Cucinella, Alessandra Lopez, Simona Zaami, Gaetano Riemma, Pierluigi Giampaolino and Giuseppe Bifulco
Cancers 2024, 16(10), 1846; https://doi.org/10.3390/cancers16101846 - 11 May 2024
Abstract
Vulvar carcinoma is a rare cancer affecting the genital tract, constituting 4% of gynecological tumors. Vulvar squamous cell carcinoma (VSCC) is the most common type. Diagnosis relies on biopsy during vulvoscopy, plus imaging such as ultrasonography (USG), magnetic resonance imaging (MRI) and positron
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Vulvar carcinoma is a rare cancer affecting the genital tract, constituting 4% of gynecological tumors. Vulvar squamous cell carcinoma (VSCC) is the most common type. Diagnosis relies on biopsy during vulvoscopy, plus imaging such as ultrasonography (USG), magnetic resonance imaging (MRI) and positron emission tomography (PET). This review aims to lay out a thorough overview as to the current preoperative management of VSCC, both in case of vulvar and lymph node involvement. The data research was conducted using the following databases: MEDLINE, EMBASE, Web of Sciences, Scopus, ClinicalTrial.gov, OVID and Cochrane Library from 2010 to 2024. The selection criteria included only original articles. Seventeen studies were assessed for eligibility. A concordance rate of 62.3% for vHSIL and 65.2% for carcinoma at vulvoscopy, with a sensitivity of 98%, specificity of 40%, PPV (Positive Predictive Value) of 37% and NPV (Negative Predictive Value) of 98% in identifying malignant lesions was found. Regarding the reliability of PET for staging and assessing lymph node involvement, a mean SUV (Standardized Uptake Value) for malignant vulvar lesions of 8.4 (range 2.5–14.7) was reported. In the case of MRI, useful for the evaluation of loco-regional infiltration and lymph node involvement, the ratio of the short-to-long-axis diameter and the reader’s diagnostic confidence for the presence of lymph node metastasis yielded accuracy of 84.8% and 86.9%, sensitivity of 86.7% and 87.5%, specificity of 81.3% and 86.2%, PPV of 89.7% and 87.5% and NPV of 76.5% and 86.2%, respectively. A long lymph node axis >10 mm and a short diameter > 5.8 mm were found to be predictors of malignancy. At USG, instead, the two main characteristics of potentially malignant lymph nodes are cortical thickness and short axis length; the combination of these ultrasound parameters yielded the highest accuracy in distinguishing between negative and positive lymph nodes. Despite the heterogeneity of the included studies and the lack of randomized clinical trials, this review provides a broad overview of the three imaging tools used for the presurgical management of VSCC. Nowadays, although MRI and PET represent the gold standard, ultrasound evaluation is taking on a growing role, as long as it is carried out by expert sonographer. The management of this rare disease should be always performed by a multidisciplinary team in order to precisely stage the tumor and determine the most suitable treatment approach.
Full article
(This article belongs to the Special Issue The Role of Medical Imaging in Gynecological Cancer)
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