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 18.2 days after submission; acceptance to publication is undertaken in 2.6 days (median values for papers published in this journal in the first 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 17 topical sections.
- Companion journals for Cancers include: Radiation and Onco.
Impact Factor:
5.2 (2022);
5-Year Impact Factor:
5.6 (2022)
Latest Articles
BRAF Mutations in Melanoma: Biological Aspects, Therapeutic Implications, and Circulating Biomarkers
Cancers 2023, 15(16), 4026; https://doi.org/10.3390/cancers15164026 - 08 Aug 2023
Abstract
Melanoma is an aggressive form of skin cancer resulting from the malignant transformation of melanocytes. Recent therapeutic approaches, including targeted therapy and immunotherapy, have improved the prognosis and outcome of melanoma patients. BRAF is one of the most frequently mutated oncogenes recognised in
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Melanoma is an aggressive form of skin cancer resulting from the malignant transformation of melanocytes. Recent therapeutic approaches, including targeted therapy and immunotherapy, have improved the prognosis and outcome of melanoma patients. BRAF is one of the most frequently mutated oncogenes recognised in melanoma. The most frequent oncogenic BRAF mutations consist of a single point mutation at codon 600 (mostly V600E) that leads to constitutive activation of the BRAF/MEK/ERK (MAPK) signalling pathway. Therefore, mutated BRAF has become a useful target for molecular therapy and the use of BRAF kinase inhibitors has shown promising results. However, several resistance mechanisms invariably develop leading to therapeutic failure. The aim of this manuscript is to review the role of BRAF mutational status in the pathogenesis of melanoma and its impact on differentiation and inflammation. Moreover, this review focuses on the mechanisms responsible for resistance to targeted therapies in BRAF-mutated melanoma and provides an overview of circulating biomarkers including circulating tumour cells, circulating tumour DNA, and non-coding RNAs.
Full article
(This article belongs to the Special Issue Targeted Therapy of Melanoma: Novel Mechanisms and Biomarkers of Drug Resistance)
Open AccessReview
Tumor Bed Boost Radiotherapy in the Conservative Treatment of Breast Cancer: A Review of Intra-Operative Techniques and Outcomes
Cancers 2023, 15(16), 4025; https://doi.org/10.3390/cancers15164025 - 08 Aug 2023
Abstract
Conservative surgery is the preferred treatment in the management of breast cancer followed by adjuvant whole-breast irradiation. Since the tumor bed is the main site of relapse, boost doses are conveniently administered according to risk factors for local relapse to increase the efficacy
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Conservative surgery is the preferred treatment in the management of breast cancer followed by adjuvant whole-breast irradiation. Since the tumor bed is the main site of relapse, boost doses are conveniently administered according to risk factors for local relapse to increase the efficacy of the treatment. The benefit of a radiation boost is well established and it can be performed by several techniques like brachytherapy, external radiation or intraoperative radiotherapy. Greater precision in localizing the tumor cavity, immediacy and increased biological response are the main advantages of intraoperative boost irradiation. This modality of treatment can be performed by means of mobile electron accelerators or low-photon X-ray devices. There is a lot of research and some published series analyzing the results of the use of an intraoperative boost as an adjuvant treatment, after neoadjuvant systemic therapy and in combination with some reconstructive surgeries. This review discusses advantages of intraoperative radiotherapy and presents the main results of a boost in terms of local control, survival, tolerance and cosmesis.
Full article
(This article belongs to the Special Issue Recent Advances and Challenges in Breast Cancer Surgery)
Open AccessReview
Pseudogenes in Cancer: State of the Art
Cancers 2023, 15(16), 4024; https://doi.org/10.3390/cancers15164024 - 08 Aug 2023
Abstract
Pseudogenes are duplicates of protein-coding genes that have accumulated multiple detrimental alterations, rendering them unable to produce the protein they encode. Initially disregarded as “junk DNA” due to their perceived lack of functionality, research on their biological roles has been hindered by this
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Pseudogenes are duplicates of protein-coding genes that have accumulated multiple detrimental alterations, rendering them unable to produce the protein they encode. Initially disregarded as “junk DNA” due to their perceived lack of functionality, research on their biological roles has been hindered by this assumption. Nevertheless, recent focus has shifted towards these molecules due to their abnormal expression in cancer phenotypes. In this review, our objective is to provide a thorough overview of the current understanding of pseudogene formation, the mechanisms governing their expression, and the roles they may play in promoting tumorigenesis.
Full article
(This article belongs to the Topic Non-coding RNAs in Cancer: Markers in Disease Progression and Therapy)
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Open AccessArticle
Synthesis and Biological Evaluation of Cyclobutane-Based β3 Integrin Antagonists: A Novel Approach to Targeting Integrins for Cancer Therapy
by
, , , , , , , and
Cancers 2023, 15(16), 4023; https://doi.org/10.3390/cancers15164023 - 08 Aug 2023
Abstract
The Arg-Gly-Asp (RGD)-binding family of integrin receptors, and notably the β3 subfamily, are key to multiple physiological processes involved in tissue development, cancer proliferation, and metastatic dissemination. While there is compelling preclinical evidence that both αvβ3 and αIIbβ3 are important anticancer targets, most
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The Arg-Gly-Asp (RGD)-binding family of integrin receptors, and notably the β3 subfamily, are key to multiple physiological processes involved in tissue development, cancer proliferation, and metastatic dissemination. While there is compelling preclinical evidence that both αvβ3 and αIIbβ3 are important anticancer targets, most integrin antagonists developed to target the β3 integrins are highly selective for αvβ3 or αIIbβ3. We report the design, synthesis, and biological evaluation of a new structural class of ligand-mimetic β3 integrin antagonist. These new antagonists combine a high activity against αvβ3 with a moderate affinity for αIIbβ3, providing the first evidence for a new approach to integrin targeting in cancer.
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(This article belongs to the Special Issue Advances in Integrins in Cancer)
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Open AccessArticle
Genetic Profiling of Cell-Free DNA in Liquid Biopsies: A Complementary Tool for the Diagnosis of B-Cell Lymphomas and the Surveillance of Measurable Residual Disease
by
, , , , , , , , , , , and
Cancers 2023, 15(16), 4022; https://doi.org/10.3390/cancers15164022 - 08 Aug 2023
Abstract
Purpose: To assess the potential value of LiqBio as a complementary tool for diagnosis and surveillance of BCL. Methods: This prospective multi-center study included 78 patients (25 follicular lymphomas (FL) and 53 large B-cell lymphomas (LBCL)). We performed next-generation sequencing (NGS) of cfDNA
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Purpose: To assess the potential value of LiqBio as a complementary tool for diagnosis and surveillance of BCL. Methods: This prospective multi-center study included 78 patients (25 follicular lymphomas (FL) and 53 large B-cell lymphomas (LBCL)). We performed next-generation sequencing (NGS) of cfDNA LiqBio and paired gDNA tissue biopsies at diagnosis and compared the mutational statuses. Also, through NGS of LiqBio, we identified MRD biomarkers and compared this novel LiqBio–MRD method with PET/CT in detecting MRD at follow-up. Results: We identified mutations in 71% of LiqBio and 95% of tissue biopsies, and found a correlation between variant allele frequency of somatic mutations. Additionally, we identified mutations in 73% of LiqBio from patients with no available tissue samples or no mutations in them. Regarding the utility of LiqBio–MRD as a dynamic monitoring tool, when compared with the PET/CT method, a lower sensitivity was observed for LiqBio–MRD at 92.3% (vs. 100% for PET/CT), but a higher specificity of 91.3% (vs. 86.9% for PET/CT). Conclusion: Genetic profiling of tumor cfDNA in plasma LiqBio is a complementary tool for BCL diagnosis and MRD surveillance.
Full article
(This article belongs to the Special Issue Measurable Residual Disease in Cancer)
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Open AccessArticle
Conventional Transarterial Chemo embolization Using Streptozocin in Patients with Unresectable Neuroendocrine Liver Metastases
by
, , , , and
Cancers 2023, 15(16), 4021; https://doi.org/10.3390/cancers15164021 - 08 Aug 2023
Abstract
Background: The purpose of this study was to evaluate the clinical, biological and radiological responses to, and tolerability of, conventional transarterial chemoembolization (cTACE) using streptozocin for unresectable neuroendocrine liver metastases. Patients and Methods: A total of 52 patients with predominant liver disease were
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Background: The purpose of this study was to evaluate the clinical, biological and radiological responses to, and tolerability of, conventional transarterial chemoembolization (cTACE) using streptozocin for unresectable neuroendocrine liver metastases. Patients and Methods: A total of 52 patients with predominant liver disease were treated with cTACE using an emulsion of streptozocin, Lipiodol and embolization particles. A sequential approach was favored in patients with high liver tumor burden. Clinical, biological and radiological responses were evaluated using carcinoid symptoms, biomarkers and mRecist criteria, respectively. Results: A total of 127 procedures were performed with a sequential approach in 65% of patients. All patients received streptozocin and Lipiodol. Carcinoid syndrome was improved in 69% of patients after treatment (p = 0.01). Post-embolization syndrome was reported in 78% of patients. At the end of all cTACE, objective response and non-progressive disease were 32% and 70%, respectively. Progression-free survival was 18.3 ± 13.3 months (median 14.9) and median overall survival (OS) from start of treatment was 74 months. The OS at 1 year, 2 years, 3 years and 5 years was 91% (IC = 84–99%), 84% (CI = 72–95%), 69% (CI = 53–84%) and 63% (C = 46–81%), respectively. Conclusions: cTACE using streptozocin is an effective and well-tolerated palliative option for patients with neuroendocrine liver metastases, associated with prolonged survival and delayed time to progression.
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(This article belongs to the Section Cancer Therapy)
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Open AccessReview
Unravelling the Complexity of Colorectal Cancer: Heterogeneity, Clonal Evolution, and Clinical Implications
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, , , , , , , , , and
Cancers 2023, 15(16), 4020; https://doi.org/10.3390/cancers15164020 - 08 Aug 2023
Abstract
Colorectal cancer (CRC) is a global health concern and a leading cause of death worldwide. The disease’s course and response to treatment are significantly influenced by its heterogeneity, both within a single lesion and between primary and metastatic sites. Biomarkers, such as mutations
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Colorectal cancer (CRC) is a global health concern and a leading cause of death worldwide. The disease’s course and response to treatment are significantly influenced by its heterogeneity, both within a single lesion and between primary and metastatic sites. Biomarkers, such as mutations in KRAS, NRAS, and BRAF, provide valuable guidance for treatment decisions in patients with metastatic CRC. While high concordance exists between mutational status in primary and metastatic lesions, some heterogeneity may be present. Circulating tumor DNA (ctDNA) analysis has proven invaluable in identifying genetic heterogeneity and predicting prognosis in RAS-mutated metastatic CRC patients. Tumor heterogeneity can arise from genetic and non-genetic factors, affecting tumor development and response to therapy. To comprehend and address clonal evolution and intratumoral heterogeneity, comprehensive genomic studies employing techniques such as next-generation sequencing and computational analysis are essential. Liquid biopsy, notably through analysis of ctDNA, enables real-time clonal evolution and treatment response monitoring. However, challenges remain in standardizing procedures and accurately characterizing tumor subpopulations. Various models elucidate the origin of CRC heterogeneity, highlighting the intricate molecular pathways involved. This review focuses on intrapatient cancer heterogeneity and genetic clonal evolution in metastatic CRC, with an emphasis on clinical applications.
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(This article belongs to the Special Issue Metastatic Colorectal Cancer 2.0)
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Open AccessArticle
A Personalized Risk Model for Azacitidine Outcome in Myelodysplastic Syndrome and Other Myeloid Neoplasms Identified by Machine Learning Model Utilizing Real-World Data
by
, , , , , , , , , , , , , , , and
Cancers 2023, 15(16), 4019; https://doi.org/10.3390/cancers15164019 - 08 Aug 2023
Abstract
Azacitidine is an approved therapy for higher-risk myelodysplastic syndrome (MDS). However, only 30–40% patients respond to azacitidine, and the responses may take up to six cycles to become evident. Delayed responses and the myelosuppressive effects of azacitidine make it challenging to predict which
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Azacitidine is an approved therapy for higher-risk myelodysplastic syndrome (MDS). However, only 30–40% patients respond to azacitidine, and the responses may take up to six cycles to become evident. Delayed responses and the myelosuppressive effects of azacitidine make it challenging to predict which patients will benefit. This is further compounded by a lack of uniform prognostic tools to identify patients at risk of early treatment failure. Hence, we performed a retrospective analysis of 273 consecutive azacytidine-treated patients. The median overall survival was 16.25 months with only 9% alive at 5 years. By using pre-treatment variables incorporated into a random forest machine learning model, we successfully identified those patients unlikely to benefit from azacytidine upfront (7.99 vs. 22.8 months, p < 0.0001). This model also identified those who required significantly more hospitalizations and transfusion support. Notably, it accurately predicted survival outcomes, outperforming the existing prognostic scoring system. By integrating somatic mutations, we further refined the model and identified three distinct risk groups with significant differences in survival (5.6 vs. 10.5 vs. 43.5 months, p < 0.0001). These real-world findings emphasize the urgent need for personalized prediction tools tailored to hypomethylating agents, reducing unnecessary complications and resource utilization in MDS treatment.
Full article
(This article belongs to the Special Issue Recent Advances in Myelodysplastic Syndromes: Diagnosis, Prognosis and Clinical Therapy)
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Open AccessArticle
Whole Exome Sequencing of Thymoma Patients Exhibiting Exceptional Responses to Pemetrexed Monotherapy
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, , , , , , , , , , , , and
Cancers 2023, 15(16), 4018; https://doi.org/10.3390/cancers15164018 - 08 Aug 2023
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Background: Pemetrexed is used for the chemotherapy of advanced thymoma. Exceptional responses of thymoma to pemetrexed treatment are not frequently observed. The underlying genetic mechanism of the exceptional responses remains unclear. We used whole-exome sequencing to explore the specific genomic aberrations that lead
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Background: Pemetrexed is used for the chemotherapy of advanced thymoma. Exceptional responses of thymoma to pemetrexed treatment are not frequently observed. The underlying genetic mechanism of the exceptional responses remains unclear. We used whole-exome sequencing to explore the specific genomic aberrations that lead to an extreme and durable response. Methods: Whole-exome sequencing using NovaSeq6000 (150 bp paired-end sequencing) was performed on nine formalin-fixed paraffin-embedded tissues from patients with advanced thymomas treated with pemetrexed (two exceptional responders and seven typical responders). Results: We identified 284 somatic single-nucleotide variants (SNVs; 272 missense, 8 missense/splice-site, 3 stop-gain, and 1 stop-gain/splice-site), 34 insertions and deletions (Indels; 33 frameshift and one splice region), and 21 copy number variations (CNVs; 15 gains and six losses). No difference in the number of SNVs variants and distribution of deleterious Indels was observed between the exceptional and typical responders. Interestingly, arm-level chromosomal CNVs (15 gains and six losses) were detected in four patients, including an exceptional responder. The highest number of arm-level CNVs was observed in an exceptional responder. Conclusion: Exceptional responders to pemetrexed for metastatic thymomas may be characterized by arm-level CNVs. Further, whole-genome and RNA sequencing studies should be performed.
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MicroRNAs Derived from Extracellular Vesicles: Keys to Understanding SARS-CoV-2 Vaccination Response in Cancer Patients?
Cancers 2023, 15(16), 4017; https://doi.org/10.3390/cancers15164017 - 08 Aug 2023
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) provoked a global pandemic identified as coronavirus disease (COVID-19), with millions of deaths worldwide. However, several important questions regarding its impact on public health remain unanswered, such as the impact of vaccination on vulnerable subpopulations such
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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) provoked a global pandemic identified as coronavirus disease (COVID-19), with millions of deaths worldwide. However, several important questions regarding its impact on public health remain unanswered, such as the impact of vaccination on vulnerable subpopulations such as cancer patients. Cytokine storm and a sustained inflammatory state are commonly associated with immune cell depletion, being manifested in most immunocompromised individuals. This strong immunosuppression can lead to a dysfunctional antiviral response to natural viral infection and compromised vaccination response. Extracellular vesicles (EVs) are membrane-bound vesicles released from cells that are involved in intercellular communication. EVs carry various molecules including microRNAs that play a crucial role in COVID-19 pathophysiology, influencing cellular responses. This review summarizes the state of the art concerning the role of EV-derived miRNAs in COVID-19 infection and their potential use as prognosis biomarkers for vaccination response in cancer patients.
Full article
(This article belongs to the Special Issue Circulating microRNAs as Biomarkers in Cancer Prognosis)
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Small Cell Lung Cancer: Emerging Targets and Strategies for Precision Therapy
by
and
Cancers 2023, 15(16), 4016; https://doi.org/10.3390/cancers15164016 - 08 Aug 2023
Abstract
Small cell lung cancer is an aggressive subtype of lung cancer with limited treatment options. Precision medicine has revolutionized cancer treatment for many tumor types but progress in SCLC has been slower due to the lack of targetable biomarkers. This review article provides
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Small cell lung cancer is an aggressive subtype of lung cancer with limited treatment options. Precision medicine has revolutionized cancer treatment for many tumor types but progress in SCLC has been slower due to the lack of targetable biomarkers. This review article provides an overview of emerging strategies for precision therapy in SCLC. Targeted therapies include targeted kinase inhibitors, monoclonal antibodies, angiogenesis inhibitors, antibody–drug conjugates, PARP inhibitors, and epigenetic modulators. Angiogenesis inhibitors and DNA-damaging agents, such as PARP and ATR inhibitors, have been explored in SCLC with limited success to date although trials are ongoing. The potential of targeting DLL3, a NOTCH ligand, through antibody–drug conjugates, bispecific T-cell engagers, and CAR T-cell therapy, has opened up new therapeutic options moving forward. Additionally, new research in epigenetic therapeutics in reversing transcriptional repression, modulating anti-tumor immunity, and utilizing antibody–drug conjugates to target cell surface-specific targets in SCLC are also being investigated. While progress in precision therapy for SCLC has been challenging, recent advancements provide optimism for improved treatment outcomes. However, several challenges remain and will need to be addressed, including drug resistance and tumor heterogeneity. Further research and biomarker-selected clinical trials are necessary to develop effective precision therapies for SCLC patients.
Full article
(This article belongs to the Special Issue Advances in Precision Medicine: Targeting Known and Emerging Oncogenic Targets in Lung Cancer)
Open AccessArticle
Deciphering Machine Learning Decisions to Distinguish between Posterior Fossa Tumor Types Using MRI Features: What Do the Data Tell Us?
Cancers 2023, 15(16), 4015; https://doi.org/10.3390/cancers15164015 - 08 Aug 2023
Abstract
Machine learning (ML) models have become capable of making critical decisions on our behalf. Nevertheless, due to complexity of these models, interpreting their decisions can be challenging, and humans cannot always control them. This paper provides explanations of decisions made by ML models
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Machine learning (ML) models have become capable of making critical decisions on our behalf. Nevertheless, due to complexity of these models, interpreting their decisions can be challenging, and humans cannot always control them. This paper provides explanations of decisions made by ML models in diagnosing four types of posterior fossa tumors: medulloblastoma, ependymoma, pilocytic astrocytoma, and brainstem glioma. The proposed methodology involves data analysis using kernel density estimations with Gaussian distributions to examine individual MRI features, conducting an analysis on the relationships between these features, and performing a comprehensive analysis of ML model behavior. This approach offers a simple yet informative and reliable means of identifying and validating distinguishable MRI features for the diagnosis of pediatric brain tumors. By presenting a comprehensive analysis of the responses of the four pediatric tumor types to each other and to ML models in a single source, this study aims to bridge the knowledge gap in the existing literature concerning the relationship between ML and medical outcomes. The results highlight that employing a simplistic approach in the absence of very large datasets leads to significantly more pronounced and explainable outcomes, as expected. Additionally, the study also demonstrates that the pre-analysis results consistently align with the outputs of the ML models and the clinical findings reported in the existing literature.
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(This article belongs to the Topic Artificial Intelligence in Cancer, Biology and Oncology)
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Open AccessEditorial
Editorial: ‘Engineering the Tumor Immune Microenvironment’ Special Issue
Cancers 2023, 15(16), 4014; https://doi.org/10.3390/cancers15164014 - 08 Aug 2023
Abstract
Cancer immunotherapies, while promising and occasionally even curative, encounter numerous hurdles within the tumor microenvironment that hinder their efficacy [...]
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(This article belongs to the Special Issue Engineering the Tumor Immune Microenvironment)
Open AccessReview
Challenges in Pharmacological Intervention in Perilipins (PLINs) to Modulate Lipid Droplet Dynamics in Obesity and Cancer
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, , , , and
Cancers 2023, 15(15), 4013; https://doi.org/10.3390/cancers15154013 - 07 Aug 2023
Abstract
Perilipins (PLINs) are the most abundant proteins in lipid droplets (LD). These LD-associated proteins are responsible for upgrading LD from inert lipid storage structures to fully functional organelles, fundamentally integrated in the lipid metabolism. There are five distinct perilipins (PLIN1–5), each with specific
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Perilipins (PLINs) are the most abundant proteins in lipid droplets (LD). These LD-associated proteins are responsible for upgrading LD from inert lipid storage structures to fully functional organelles, fundamentally integrated in the lipid metabolism. There are five distinct perilipins (PLIN1–5), each with specific expression patterns and metabolic activation, but all capable of regulating the activity of lipases on LD. This plurality creates a complex orchestrated mechanism that is directly related to the healthy balance between lipogenesis and lipolysis. Given the essential role of PLINs in the modulation of the lipid metabolism, these proteins can become interesting targets for the treatment of lipid-associated diseases. Since reprogrammed lipid metabolism is a recognized cancer hallmark, and obesity is a known risk factor for cancer and other comorbidities, the modulation of PLINs could either improve existing treatments or create new opportunities for the treatment of these diseases. Even though PLINs have not been, so far, directly considered for pharmacological interventions, there are many established drugs that can modulate PLINs activity. Therefore, the aim of this study is to assess the involvement of PLINs in diseases related to lipid metabolism dysregulation and whether PLINs can be viewed as potential therapeutic targets for cancer and obesity.
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(This article belongs to the Section Cancer Pathophysiology)
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Maintenance Chemotherapy for Patients with Rhabdomyosarcoma
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, , , , , , , , and
Cancers 2023, 15(15), 4012; https://doi.org/10.3390/cancers15154012 - 07 Aug 2023
Abstract
Maintenance chemotherapy (MC) defines the administration of prolonged relatively low-intensity chemotherapy with the aim of “maintaining” tumor complete remission. This paper aims to report an update of the RMS2005 trial, which demonstrated better survival for patients with high-risk localized rhabdomyosarcoma (RMS) when MC
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Maintenance chemotherapy (MC) defines the administration of prolonged relatively low-intensity chemotherapy with the aim of “maintaining” tumor complete remission. This paper aims to report an update of the RMS2005 trial, which demonstrated better survival for patients with high-risk localized rhabdomyosarcoma (RMS) when MC with vinorelbine and low-dose cyclophosphamide was added to standard chemotherapy, and to discuss the published experience on MC in RMS. In the RMS2005 study, the outcome for patients receiving MC vs. those who stopped the treatment remains superior, with a 5-year disease-free survival of 78.1% vs. 70.1% (p = 0.056) and overall survival of 85.0% vs. 72.4% (p = 0.008), respectively. We found seven papers describing MC in RMS, but only one randomized trial that did not demonstrate any advantage when MC with eight courses of trofosfamide/idarubicine alternating with trofosfamide/etoposide has been employed in high-risk RMS. The use of MC showed better results in comparison to high-dose chemotherapy in non-randomized studies, including metastatic patients, and demonstrated feasibility and tolerability in relapsed RMS. Many aspects of MC in RMS need to be investigated, including the best drug combination and the optimal duration. The ongoing EpSSG trial will try to answer some of these questions.
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(This article belongs to the Special Issue Improving Treatment for Rhabdomyosarcoma: A Collaborative Approach through the European Paediatric Soft Tissue Sarcoma Study Group (EpSSG))
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Influence of De Novo Malignancies on Long-Term Survival after Lung Transplantation
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, , , , , , and
Cancers 2023, 15(15), 4011; https://doi.org/10.3390/cancers15154011 - 07 Aug 2023
Abstract
(1) Background: Malignancies are an important cause of mortality after solid organ transplantation. The purpose of this study was to analyze the incidence of malignancies in patients receiving lung transplants (LT) and their influence on patients’ survival. (2) Methods: Review of consecutive LT
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(1) Background: Malignancies are an important cause of mortality after solid organ transplantation. The purpose of this study was to analyze the incidence of malignancies in patients receiving lung transplants (LT) and their influence on patients’ survival. (2) Methods: Review of consecutive LT from 1994 to 2021. Patients with and without malignancies were compared by univariable and multivariable analyses. Survival was compared with Kaplan-Meier and Cox regression analysis. (3) Results: There were 731 LT malignancies developed in 91 patients (12.4%) with related mortality of 47% (n = 43). Native lung cancer, digestive and hematological malignancies were associated with higher lethality. Malignancies were more frequent in males (81%; p = 0.005), transplanted for emphysema (55%; p = 0.003), with cyclosporine-based immunosuppression (58%; p < 0.001), and receiving single LT (65%; p = 0.011). Survival was worse in patients with malignancies (overall) and with native lung cancer. Risk factors for mortality were cyclosporine-based immunosuppression (OR 1.8; 95%CI: 1.3–2.4; p < 0.001) and de novo lung cancer (OR 2.6; 95%CI: 1.5–4.4; p < 0.001). (4) Conclusions: Malignancies are an important source of morbidity and mortality following lung transplantation that should not be neglected. Patients undergoing single LT for emphysema are especially at higher risk of mortality due to lung cancer in the native lung.
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(This article belongs to the Special Issue Lung Transplantation and Lung Cancer: Clinical Scenarios, Outcomes and Future Perspectives)
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Open AccessArticle
YY1 Knockdown Relieves the Differentiation Block and Restores Apoptosis in AML Cells
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, , , , , , , , , , , and
Cancers 2023, 15(15), 4010; https://doi.org/10.3390/cancers15154010 - 07 Aug 2023
Abstract
In this study we analyzed the expression of Yin and Yang 1 protein (YY1), a member of the noncanonical PcG complexes, in AML patient samples and AML cell lines and the effect of YY1 downregulation on the AML differentiation block. Our results show
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In this study we analyzed the expression of Yin and Yang 1 protein (YY1), a member of the noncanonical PcG complexes, in AML patient samples and AML cell lines and the effect of YY1 downregulation on the AML differentiation block. Our results show that YY1 is significantly overexpressed in AML patient samples and AML cell lines and that YY1 knockdown relieves the differentiation block. YY1 downregulation in two AML cell lines (HL-60 and OCI-AML3) and one AML patient sample restored the expression of members of the CEBP protein family, increased the expression of extrinsic growth factors/receptors and surface antigenic markers, induced morphological cell characteristics typical of myeloid differentiation, and sensitized cells to retinoic acid treatment and to apoptosis. Overall, our data show that YY1 is not a secondary regulator of myeloid differentiation but that, if overexpressed, it can play a predominant role in myeloid differentiation block.
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(This article belongs to the Section Molecular Cancer Biology)
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Open AccessReview
From Circulating Tumor Cells to Mirna: New Challenges in the Diagnosis and Prognosis of Medullary Thyroid Cancer
Cancers 2023, 15(15), 4009; https://doi.org/10.3390/cancers15154009 - 07 Aug 2023
Abstract
Medullary thyroid carcinoma (MTC) is a malignant tumor that arises from parafollicular C cells, which are responsible for producing calcitonin. The majority (75%) of MTC cases are sporadic forms, while the remaining (25%) have a hereditary component. In these hereditary cases, MTC can
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Medullary thyroid carcinoma (MTC) is a malignant tumor that arises from parafollicular C cells, which are responsible for producing calcitonin. The majority (75%) of MTC cases are sporadic forms, while the remaining (25%) have a hereditary component. In these hereditary cases, MTC can occur in conjunction with other endocrine disorders (i.e., pheochromocytoma) or as an isolated condition known as familial medullary thyroid carcinoma. The primary genetic mutation associated with the development of MTC, regardless of its hereditary or sporadic nature, is a point mutation in the RET gene. Evaluation of serum calcitonin levels represents the most reliable and sensitive marker for both the initial diagnosis and the postsurgical monitoring of MTC. Unfortunately, most patients do not achieve normalization of postsurgical serum calcitonin (CT) levels after surgery. Therefore, there is a need to find new biomarkers to be used with serum CT in order to increase test sensitivity and specificity. In this review, we summarize the literature from 2010 to 2023 to review the role of circulating tumor cells, cell-free DNA, and miRNA and their application in diagnosis, outcome of MTC, and response to treatments.
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(This article belongs to the Special Issue The Molecular Basis of Thyroid Cancer)
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Assessing Osteolytic Lesion Size on Sequential CT Scans Is a Reliable Study Endpoint for Bone Remineralization in Newly Diagnosed Multiple Myeloma
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, , , , , , , , and
Cancers 2023, 15(15), 4008; https://doi.org/10.3390/cancers15154008 - 07 Aug 2023
Abstract
Multiple myeloma (MM) frequently induces persisting osteolytic manifestations despite hematologic treatment response. This study aimed to establish a biometrically valid study endpoint for bone remineralization through quantitative and qualitative analyses in sequential CT scans. Twenty patients (seven women, 58 ± 8 years) with
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Multiple myeloma (MM) frequently induces persisting osteolytic manifestations despite hematologic treatment response. This study aimed to establish a biometrically valid study endpoint for bone remineralization through quantitative and qualitative analyses in sequential CT scans. Twenty patients (seven women, 58 ± 8 years) with newly diagnosed MM received standardized induction therapy comprising the anti-SLAMF7 antibody elotuzumab, carfilzomib, lenalidomide, and dexamethasone (E-KRd). All patients underwent whole-body low-dose CT scans before and after six cycles of E-KRd. Two radiologists independently recorded osteolytic lesion sizes, as well as the presence of cortical destruction, pathologic fractures, rim and trabecular sclerosis. Bland–Altman analyses and Krippendorff’s α were employed to assess inter-reader reliability, which was high for lesion size measurement (standard error 1.2 mm) and all qualitative criteria assessed (α ≥ 0.74). After six cycles of E-KRd induction, osteolytic lesion size decreased by 22% (p < 0.001). While lesion size response did not correlate with the initial lesion size at baseline imaging (Pearson’s r = 0.144), logistic regression analysis revealed that the majority of responding osteolyses exhibited trabecular sclerosis (p < 0.001). The sum of osteolytic lesion sizes on sequential CT scans defines a reliable study endpoint to characterize bone remineralization. Patient level response is strongly associated with the presence of trabecular sclerosis.
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(This article belongs to the Special Issue Advanced Research in Multiple Myeloma, Volume II)
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Deep Transfer Learning with Enhanced Feature Fusion for Detection of Abnormalities in X-ray Images
Cancers 2023, 15(15), 4007; https://doi.org/10.3390/cancers15154007 - 07 Aug 2023
Abstract
Medical image classification poses significant challenges in real-world scenarios. One major obstacle is the scarcity of labelled training data, which hampers the performance of image-classification algorithms and generalisation. Gathering sufficient labelled data is often difficult and time-consuming in the medical domain, but deep
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Medical image classification poses significant challenges in real-world scenarios. One major obstacle is the scarcity of labelled training data, which hampers the performance of image-classification algorithms and generalisation. Gathering sufficient labelled data is often difficult and time-consuming in the medical domain, but deep learning (DL) has shown remarkable performance, although it typically requires a large amount of labelled data to achieve optimal results. Transfer learning (TL) has played a pivotal role in reducing the time, cost, and need for a large number of labelled images. This paper presents a novel TL approach that aims to overcome the limitations and disadvantages of TL that are characteristic of an ImageNet dataset, which belongs to a different domain. Our proposed TL approach involves training DL models on numerous medical images that are similar to the target dataset. These models were then fine-tuned using a small set of annotated medical images to leverage the knowledge gained from the pre-training phase. We specifically focused on medical X-ray imaging scenarios that involve the humerus and wrist from the musculoskeletal radiographs (MURA) dataset. Both of these tasks face significant challenges regarding accurate classification. The models trained with the proposed TL were used to extract features and were subsequently fused to train several machine learning (ML) classifiers. We combined these diverse features to represent various relevant characteristics in a comprehensive way. Through extensive evaluation, our proposed TL and feature-fusion approach using ML classifiers achieved remarkable results. For the classification of the humerus, we achieved an accuracy of 87.85%, an F1-score of 87.63%, and a Cohen’s Kappa coefficient of 75.69%. For wrist classification, our approach achieved an accuracy of 85.58%, an F1-score of 82.70%, and a Cohen’s Kappa coefficient of 70.46%. The results demonstrated that the models trained using our proposed TL approach outperformed those trained with ImageNet TL. We employed visualisation techniques to further validate these findings, including a gradient-based class activation heat map (Grad-CAM) and locally interpretable model-independent explanations (LIME). These visualisation tools provided additional evidence to support the superior accuracy of models trained with our proposed TL approach compared to those trained with ImageNet TL. Furthermore, our proposed TL approach exhibited greater robustness in various experiments compared to ImageNet TL. Importantly, the proposed TL approach and the feature-fusion technique are not limited to specific tasks. They can be applied to various medical image applications, thus extending their utility and potential impact. To demonstrate the concept of reusability, a computed tomography (CT) case was adopted. The results obtained from the proposed method showed improvements.
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(This article belongs to the Special Issue Recent Advances in Deep Learning and Medical Imaging for Cancer Treatment)
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