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 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
Clinical Use of a Commercial Artificial Intelligence-Based Software for Autocontouring in Radiation Therapy: Geometric Performance and Dosimetric Impact
Cancers 2023, 15(24), 5735; https://doi.org/10.3390/cancers15245735 (registering DOI) - 07 Dec 2023
Abstract
Purpose: When autocontouring based on artificial intelligence (AI) is used in the radiotherapy (RT) workflow, the contours are reviewed and eventually adjusted by a radiation oncologist before an RT treatment plan is generated, with the purpose of improving dosimetry
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Purpose: When autocontouring based on artificial intelligence (AI) is used in the radiotherapy (RT) workflow, the contours are reviewed and eventually adjusted by a radiation oncologist before an RT treatment plan is generated, with the purpose of improving dosimetry and reducing both interobserver variability and time for contouring. The purpose of this study was to evaluate the results of application of a commercial AI-based autocontouring for RT, assessing both geometric accuracies and the influence on optimized dose from automatically generated contours after review by human operator. Materials and Methods: A commercial autocontouring system was applied to a retrospective database of 40 patients, of which 20 were treated with radiotherapy for prostate cancer (PCa) and 20 for head and neck cancer (HNC). Contours resulting from AI were compared against AI contours reviewed by human operator and human-only contours using Dice similarity coefficient (DSC), Hausdorff distance (HD), and relative volume difference (RVD). Dosimetric indices such as Dmean, D0.03cc, and normalized plan quality metrics were used to compare dose distributions from RT plans generated from structure sets contoured by humans assisted by AI against plans from manual contours. The reduction in contouring time obtained by using automated tools was also assessed. A Wilcoxon rank sum test was computed to assess the significance of differences. Interobserver variability of the comparison of manual vs. AI-assisted contours was also assessed among two radiation oncologists for PCa. Results: For PCa, AI-assisted segmentation showed good agreement with expert radiation oncologist structures with average DSC among patients ≥ 0.7 for all structures, and minimal radiation oncology adjustment of structures (DSC of adjusted versus AI structures ≥ 0.91). For HNC, results of comparison between manual and AI contouring varied considerably e.g., 0.77 for oral cavity and 0.11–0.13 for brachial plexus, but again, adjustment was generally minimal (DSC of adjusted against AI contours 0.97 for oral cavity, 0.92–0.93 for brachial plexus). The difference in dose for the target and organs at risk were not statistically significant between human and AI-assisted, with the only exceptions of D0.03cc to the anal canal and Dmean to the brachial plexus. The observed average differences in plan quality for PCa and HNC cases were 8% and 6.7%, respectively. The dose parameter changes due to interobserver variability in PCa were small, with the exception of the anal canal, where large dose variations were observed. The reduction in time required for contouring was 72% for PCa and 84% for HNC. Conclusions: When an autocontouring system is used in combination with human review, the time of the RT workflow is significantly reduced without affecting dose distribution and plan quality.
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(This article belongs to the Special Issue Radiomics and Imaging in Cancer Analysis)
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Urinary, Gastrointestinal, and Sexual Dysfunctions after Chemotherapy, Radiotherapy, Radical Surgery or Multimodal Treatment in Women with Locally Advanced Cervical Cancer: A Multicenter Retrospective Study
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, , , , , , , , , , and
Cancers 2023, 15(24), 5734; https://doi.org/10.3390/cancers15245734 (registering DOI) - 07 Dec 2023
Abstract
Background: Different strategies have been proposed for the treatment of locally advanced cervical cancer (LACC), with different impacts on patient’s quality of life (QoL). This study aimed to analyze urinary, bowel, and sexual dysfunctions in a series of LACC patients who underwent chemotherapy,
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Background: Different strategies have been proposed for the treatment of locally advanced cervical cancer (LACC), with different impacts on patient’s quality of life (QoL). This study aimed to analyze urinary, bowel, and sexual dysfunctions in a series of LACC patients who underwent chemotherapy, radiotherapy, radical surgery, or a combination of these treatments. Methods: Patients with LACC who underwent neoadjuvant radio–chemotherapy (NART/CT; n = 35), neoadjuvant chemotherapy (NACT; n = 17), exclusive radio–chemotherapy (ERT/CT; n = 28), or upfront surgery (UPS; n = 10) from November 2010 to September 2019 were identified from five oncological referral centers. A customized questionnaire was used for the valuation of urinary, gastrointestinal, and sexual dysfunctions. Results: A total of 90 patients were included. Increased urinary frequency (>8 times/day) was higher in ERT/CT compared with NACT/RT (57.1% vs. 28.6%; p = 0.02) and NACT (57.1% vs. 17.6%; p = 0.01). The use of sanitary pads for urinary leakage was higher in ERT/CT compared with NACT/RT (42.9% vs. 14.3%; p = 0.01) and NACT (42.9% vs. 11.8%; p = 0.03). The rate of reduced evacuations (<3 times a week) was less in UPS compared with NACT/RT (50% vs. 97.1%; p < 0.01), NACT (50% vs. 88.2, p < 0.01), and ERT/CT (50% vs. 96.4%; p < 0.01). A total of 52 women were not sexually active after therapy, and pain was the principal reason for the avoidance of sexual activity. Conclusions: The rate and severity of urinary, gastrointestinal, and sexual dysfunction were similar in the four groups of treatment. Nevertheless, ERT/CT was associated with worse sexual and urinary outcomes.
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(This article belongs to the Special Issue Advancements in Surgical Approaches for Gynecological Cancers)
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Strategy for Pediatric Patients with Relapsed or Refractory Anaplastic Lymphoma Kinase-Positive Anaplastic Large Cell Lymphoma: A Review
by
and
Cancers 2023, 15(24), 5733; https://doi.org/10.3390/cancers15245733 (registering DOI) - 07 Dec 2023
Abstract
Anaplastic lymphoma kinase (ALK)-positive anaplastic large cell lymphoma (ALCL) is an aggressive T-cell lymphoma characterized by large T-cells with strong CD30 and ALK expression. Although conventional chemotherapy is effective in most patients, approximately 30% experience a relapse or refractory disease and have a
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Anaplastic lymphoma kinase (ALK)-positive anaplastic large cell lymphoma (ALCL) is an aggressive T-cell lymphoma characterized by large T-cells with strong CD30 and ALK expression. Although conventional chemotherapy is effective in most patients, approximately 30% experience a relapse or refractory disease and have a poor prognosis. Several risk factors associated with poor prognosis have been identified in pediatric ALK-positive ALCL. These include morphological patterns with the small cell variant or lymphohistiocytic variant, leukemic presentation, the presence of minimal disseminated disease, or involvement of the central nervous system. Relapsed or refractory ALK-positive ALCL is often resistant to conventional chemotherapy; therefore, salvage therapy is required. In recent years, targeted therapies such as ALK inhibitors and brentuximab vedotin (BV) have been developed. ALK inhibitors block the continuous activation of ALK kinase, a driver mutation that leads to cell proliferation in ALK-positive ALCL. Additionally, BV is an antibody–drug conjugate that targets CD30-positive cells. Both ALK inhibitors and BV have displayed dramatic effects in chemoresistant ALK-positive ALCL. Weekly vinblastine treatment and hematopoietic stem cell transplantation have also been reported to be effective therapies. This article reviews pediatric ALK-positive ALCL, focusing on risk factors and treatment strategies for pediatric patients with relapsed or refractory ALK-positive ALCL.
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(This article belongs to the Special Issue Pediatric Cancer: From Molecular Targets to Effective Therapies)
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Telomere Maintenance Mechanisms in a Cohort of High-Risk Neuroblastoma Tumors and Its Relation to Genomic Variants in the TERT and ATRX Genes
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, , , , , , , , , , , , and
Cancers 2023, 15(24), 5732; https://doi.org/10.3390/cancers15245732 (registering DOI) - 07 Dec 2023
Abstract
Tumor cells are hallmarked by their capacity to undergo unlimited cell divisions, commonly accomplished either by mechanisms that activate TERT or through the alternative lengthening of telomeres pathway. Neuroblastoma is a heterogeneous pediatric cancer, and the aim of this study was to characterize
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Tumor cells are hallmarked by their capacity to undergo unlimited cell divisions, commonly accomplished either by mechanisms that activate TERT or through the alternative lengthening of telomeres pathway. Neuroblastoma is a heterogeneous pediatric cancer, and the aim of this study was to characterize telomere maintenance mechanisms in a high-risk neuroblastoma cohort. All tumor samples were profiled with SNP microarrays and, when material was available, subjected to whole genome sequencing (WGS). Telomere length was estimated from WGS data, samples were assayed for the ALT biomarker c-circles, and selected samples were subjected to methylation array analysis. Samples with ATRX aberration in this study were positive for c-circles, whereas samples with either MYCN amplification or TERT re-arrangement were negative for c-circles. Both ATRX aberrations and TERT re-arrangement were enriched in 11q-deleted samples. An association between older age at diagnosis and 1q-deletion was found in the ALT-positive group. TERT was frequently placed in juxtaposition to a previously established gene in neuroblastoma tumorigenesis or cancer in general. Given the importance of high-risk neuroblastoma, means for mitigating active telomere maintenance must be therapeutically explored.
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(This article belongs to the Section Pediatric Oncology)
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Pleural Mesothelioma: Treatable Traits of a Heterogeneous Disease
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, , , , , , , , , , , and
Cancers 2023, 15(24), 5731; https://doi.org/10.3390/cancers15245731 - 06 Dec 2023
Abstract
Pleural mesothelioma is an aggressive disease with diffuse nature, low median survival, and prolonged latency presenting difficulty in prognosis, diagnosis, and treatment. Here, we review all these aspects to underline the progress being made in its investigation and to emphasize how much work
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Pleural mesothelioma is an aggressive disease with diffuse nature, low median survival, and prolonged latency presenting difficulty in prognosis, diagnosis, and treatment. Here, we review all these aspects to underline the progress being made in its investigation and to emphasize how much work remains to be carried out to improve prognosis and treatment.
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(This article belongs to the Special Issue Mesothelioma—from Diagnosis to Treatment)
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Detection of Germline Mutations in a Cohort of 250 Relatives of Mutation Carriers in Multigene Panel: Impact of Pathogenic Variants in Other Genes beyond BRCA1/2
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, , , , , , , , , , , and
Cancers 2023, 15(24), 5730; https://doi.org/10.3390/cancers15245730 (registering DOI) - 06 Dec 2023
Abstract
Background: Several hereditary–familial syndromes associated with various types of tumors have been identified to date, evidencing that hereditary cancers caused by germline mutations account for 5–10% of all tumors. Advances in genetic technology and the implementation of Next-Generation Sequencing (NGS) have accelerated the
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Background: Several hereditary–familial syndromes associated with various types of tumors have been identified to date, evidencing that hereditary cancers caused by germline mutations account for 5–10% of all tumors. Advances in genetic technology and the implementation of Next-Generation Sequencing (NGS) have accelerated the discovery of several susceptibility cancer genes, allowing for the detection of cancer-predisposing mutations in a larger number of cases. The aim of this study is to highlight how the application of an NGS-multigene panel to a group of oncological patients subsequently leads to improvement in the identification of carriers of healthy pathogenic variants/likely pathogenic variants (PVs/LPVs) and prevention of the disease in these cases. Methods: Starting from a total of 110 cancer patients carrying PVs/LPVs in genes involved in cancer susceptibility detected via a customized NGS panel of 27 cancer-associated genes, we enrolled 250 healthy collateral family members from January 2020 to July 2022. The specific PVs/LPVs identified in each proband were tested in healthy collateral family members via Sanger sequencing. Results: A total of 131 out of the 250 cases (52%) were not carriers of the mutation detected in the affected relative, while 119 were carriers. Of these, 81/250 patients carried PVs/LPVs on BRCA1/2 (33%), 35/250 harbored PVs/LPVs on other genes beyond BRCA1 and BRCA2 (14%), and 3/250 (1%) were PVs/LPVs carriers both on BRCA1/2 and on another susceptibility gene. Conclusion: Our results show that the analysis of BRCA1/2 genes would have only resulted in a missed diagnosis in a number of cases and in the lack of prevention of the disease in a considerable percentage of healthy carriers with a genetic mutation (14%).
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(This article belongs to the Section Cancer Causes, Screening and Diagnosis)
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A Comparative Multicenter Cohort Study Evaluating the Long-Term Influence of the Strict Lockdown during the First COVID-19 Wave on Lung Cancer Patients (ARTEMISIA Trial)
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, , , , , , , , and
Cancers 2023, 15(24), 5729; https://doi.org/10.3390/cancers15245729 - 06 Dec 2023
Abstract
The consequences of the strict health restrictions during the first wave of COVID-19 on lung cancer (LC) patients are not known. This cohort study evaluated the impact of the initial lockdown on management of and long-term outcome in LC patients. This exposed–unexposed-type study
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The consequences of the strict health restrictions during the first wave of COVID-19 on lung cancer (LC) patients are not known. This cohort study evaluated the impact of the initial lockdown on management of and long-term outcome in LC patients. This exposed–unexposed-type study included two evaluation periods of 6 months each in non-selected patients; one began on the first day of lockdown in 2020, and the other in 2019 during the same calendar period. Various indicators were compared: clinical profiles, management delays and overall survival beyond 2 years. A total of 816 patients from 7 public or private centers were enrolled. The clinical characteristics of the patients in 2020 did not differ from those in 2019, except that the population was older (p = 0.002) with more non-smokers (p = 0.006). Delays for pre-therapeutic medical management were generally reduced after the first imaging in 2020 (1.28 [1.1–1.49]). In the multivariate analysis, being part of the 2020 cohort was correlated with better prognosis (HR = 0.71 [0.5–0.84], p < 0.001). The gain observed in 2020 mainly benefited non-smoking patients, along with ECOG PS 0–2 (p = 0.01), stage 4 (p = 0.003), squamous cell carcinoma (p = 0.03) and receiving systemic therapy (p = 0.03). In conclusion, the first lockdown did not exert any deleterious impact on LC patients.
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(This article belongs to the Collection The Impact of COVID-19 Infection in Cancer)
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Unleashing the Power of Yes-Associated Protein in Ferroptosis and Drug Resistance in Breast Cancer, with a Special Focus on Therapeutic Strategies
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, , , and
Cancers 2023, 15(24), 5728; https://doi.org/10.3390/cancers15245728 - 06 Dec 2023
Abstract
The YAP protein is a critical oncogenic mediator within the Hippo signaling pathway and has been implicated in various cancer types. In breast cancer, it frequently becomes activated, thereby contributing to developing drug-resistance mechanisms. Recent studies have underscored the intricate interplay between YAP
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The YAP protein is a critical oncogenic mediator within the Hippo signaling pathway and has been implicated in various cancer types. In breast cancer, it frequently becomes activated, thereby contributing to developing drug-resistance mechanisms. Recent studies have underscored the intricate interplay between YAP and ferroptosis within the breast tumor microenvironment. YAP exerts a negative regulatory effect on ferroptosis, promoting cancer cell survival and drug resistance. This review offers a concise summary of the current understanding surrounding the interplay between the YAP pathway, ferroptosis, and drug-resistance mechanisms in both bulk tumor cells and cancer stem cells. We also explore the potential of natural compounds alone or in combination with anticancer therapies for targeting the YAP pathway in treating drug-resistant breast cancer. This approach holds the promise of enhancing the effectiveness of current treatments and paving the way for developing novel therapeutics.
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(This article belongs to the Special Issue Overcoming Drug Resistance to Systemic Therapy in Breast Cancer)
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Inhibition of DHODH Enhances Replication-Associated Genomic Instability and Promotes Sensitivity in Endometrial Cancer
Cancers 2023, 15(24), 5727; https://doi.org/10.3390/cancers15245727 - 06 Dec 2023
Abstract
Endometrial carcinoma (EC) is the most common gynecological malignancy in the United States. De novo pyrimidine synthesis pathways generate nucleotides that are required for DNA synthesis. Approximately 38% of human endometrial tumors present with an overexpression of human dihydroorotate dehydrogenase (DHODH). However, the
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Endometrial carcinoma (EC) is the most common gynecological malignancy in the United States. De novo pyrimidine synthesis pathways generate nucleotides that are required for DNA synthesis. Approximately 38% of human endometrial tumors present with an overexpression of human dihydroorotate dehydrogenase (DHODH). However, the role of DHODH in cancer cell DNA replication and its impact on modulating a treatment response is currently unknown. Here, we report that endometrial tumors with overexpression of DHODH are associated with a high mutation count and chromosomal instability. Furthermore, tumors with an overexpression of DHODH show significant co-occurrence with mutations in DNA replication polymerases, which result in a histologically high-grade endometrial tumor. An in vitro experiment demonstrated that the inhibition of DHODH in endometrial cancer cell lines significantly induced replication-associated DNA damage and hindered replication fork progression. Furthermore, endometrial cancer cells were sensitive to the DHODH inhibitor either alone or in combination with the Poly (ADP-ribose) polymerase 1 inhibitor. Our findings may have important clinical implications for utilizing DHODH as a potential target to enhance cytotoxicity in high-grade endometrial tumors.
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(This article belongs to the Collection Incorporating DNA Damage Response (DDR) Mechanisms in Cancer Systems)
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“Things Have Changed”—Laparoscopic Cytoreduction for Advanced and Recurrent Ovarian Cancer: The Experience of a Referral Center on 108 Patients
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, , , , , , , , , , , and
Cancers 2023, 15(24), 5726; https://doi.org/10.3390/cancers15245726 - 06 Dec 2023
Abstract
Objective: To report the feasibility of laparoscopic cytoreduction surgery for primary and recurrent ovarian cancer in a select group of patients. Methods: A retrospective analysis was conducted on a cohort of patients with FIGO stage IIIA-IV advanced ovarian cancer who underwent laparoscopic primary
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Objective: To report the feasibility of laparoscopic cytoreduction surgery for primary and recurrent ovarian cancer in a select group of patients. Methods: A retrospective analysis was conducted on a cohort of patients with FIGO stage IIIA-IV advanced ovarian cancer who underwent laparoscopic primary debulking surgery (PDS), interval debulking surgery (IDS), or secondary debulking surgery (SDS) between June 2008 and January 2020. The primary endpoint was achieving optimal cytoreduction, defined as residual tumor less than 1 cm. Secondary endpoints included evaluating surgical complications and long-term survival, assessed at three-month intervals during the initial two years and then every six months. Results: This study included a total of 108 patients, among whom, 40 underwent PDS, 44 underwent IDS, and 24 underwent SDS. Optimal cytoreduction rates were found to be 95.0%, 97.7%, and 95.8% for the PDS, ISD, and SDS groups, respectively. Early postoperative complications (<30 days from surgery) occurred in 19.2% of cases, with 7.4% of these cases requiring reintervention. One patient died following postoperative respiratory failure. Late postoperative complications (<30 days from surgery) occurred in 9.3% of cases, and they required surgical reintervention only in one case. After laparoscopic optimal cytoreduction with a median follow-up time of 25 months, the overall recurrence rates were 45.7%, 38.5%, and 39.3% for PDS, ISD, and SDS, respectively. The three-year overall survival rates were 84%, 66%, and 63%, respectively, while the three-year disease-free survival rates were 48%, 51%, and 71%, respectively. Conclusions: Laparoscopic cytoreduction surgery is feasible for advanced ovarian cancer in carefully selected patients, resulting in high rates of optimal cytoreduction, satisfactory peri-operative morbidity, and encouraging survival outcomes. Future studies should focus on establishing standardized selection criteria and conducting well-designed investigations to further refine patient selection and evaluate long-term outcomes.
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(This article belongs to the Special Issue Gynecologic Cancer: From Diagnosis to Treatment)
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Gastro-Esophageal Junction Precancerosis: Histological Diagnostic Approach and Pathogenetic Insights
Cancers 2023, 15(24), 5725; https://doi.org/10.3390/cancers15245725 - 06 Dec 2023
Abstract
Barrett’s esophagus (BE) was initially defined in the 1950s as the visualization of gastric-like mucosa in the esophagus. Over time, the definition has evolved to include the identification of goblet cells, which confirm the presence of intestinal metaplasia within the esophagus. Chronic gastro-esophageal
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Barrett’s esophagus (BE) was initially defined in the 1950s as the visualization of gastric-like mucosa in the esophagus. Over time, the definition has evolved to include the identification of goblet cells, which confirm the presence of intestinal metaplasia within the esophagus. Chronic gastro-esophageal reflux disease (GERD) is a significant risk factor for adenocarcinoma of the esophagus, as intestinal metaplasia can develop due to GERD. The development of adenocarcinomas related to BE progresses in sequence from inflammation to metaplasia, dysplasia, and ultimately carcinoma. In the presence of GERD, the squamous epithelium changes to columnar epithelium, which initially lacks goblet cells, but later develops goblet cell metaplasia and eventually dysplasia. The accumulation of multiple genetic and epigenetic alterations leads to the development and progression of dysplasia. The diagnosis of BE requires the identification of intestinal metaplasia on histologic examination, which has thus become an essential tool both in the diagnosis and in the assessment of dysplasia’s presence and degree. The histologic diagnosis of BE dysplasia can be challenging due to sampling error, pathologists’ experience, interobserver variation, and difficulty in histologic interpretation: all these problems complicate patient management. The development and progression of Barrett’s esophagus (BE) depend on various molecular events that involve changes in cell-cycle regulatory genes, apoptosis, cell signaling, and adhesion pathways. In advanced stages, there are widespread genomic abnormalities with losses and gains in chromosome function, and DNA instability. This review aims to provide an updated and comprehensible diagnostic approach to BE based on the most recent guidelines available in the literature, and an overview of the pathogenetic and molecular mechanisms of its development.
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(This article belongs to the Special Issue Feature Review Papers on Gastroesophageal Junction and Gastric Cancers)
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Beta-Hydroxybutyrate Augments Oxaliplatin-Induced Cytotoxicity by Altering Energy Metabolism in Colorectal Cancer Organoids
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, , , , and
Cancers 2023, 15(24), 5724; https://doi.org/10.3390/cancers15245724 - 06 Dec 2023
Abstract
Deregulation of cellular metabolism has recently emerged as a notable cancer characteristic. This reprogramming of key metabolic pathways supports tumor growth. Targeting cancer metabolism demonstrates the potential for managing colorectal cancer. Beta-hydroxybutyrate (BOHB) acts as an acetyl-CoA source for the tricarboxylic acid (TCA)
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Deregulation of cellular metabolism has recently emerged as a notable cancer characteristic. This reprogramming of key metabolic pathways supports tumor growth. Targeting cancer metabolism demonstrates the potential for managing colorectal cancer. Beta-hydroxybutyrate (BOHB) acts as an acetyl-CoA source for the tricarboxylic acid (TCA) cycle, possibly redirecting energy metabolic pathways towards the TCA cycle that could enhance sensitivity to oxaliplatin, through the generation of reactive oxygen species (ROS). This study explores the potential of BOHB to enhance oxaliplatin’s cytotoxic effect by altering the energy metabolism in colorectal cancer. The study employed advanced in vitro organoid technology, which successfully emulates in vivo physiology. The combination treatment efficacy of BOHB and oxaliplatin was evaluated via cell viability assay. The levels of key proteins involved in energy metabolism, apoptotic pathways, DNA damage markers, and histone acetylation were analyzed via Western Blot. ROS levels were evaluated via flow cytometer. Non-toxic doses of BOHB with oxaliplatin significantly amplified cytotoxicity in colorectal cancer organoids. Treatment with BOHB and/or melatonin resulted in significantly decreased lactate dehydrogenase A and increased mitochondrial carrier protein 2 levels, indicating inhibited aerobic glycolysis and an increased oxidative phosphorylation rate. This metabolic shift induced apoptotic cell death mediated by oxaliplatin, owing to high levels of ROS. Melatonin counteracted this effect by protecting cancer cells from high oxidative stress conditions. BOHB may enhance the efficacy of chemotherapeutics with a similar mechanism of action to oxaliplatin in colorectal cancer treatment. These innovative combinations could improve treatment outcomes for colorectal cancer patients.
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(This article belongs to the Topic Advances in Colorectal Cancer Therapy)
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Cardiac Arrhythmias in Patients Treated for Lung Cancer: A Review
Cancers 2023, 15(24), 5723; https://doi.org/10.3390/cancers15245723 - 06 Dec 2023
Abstract
Cardio-oncology currently faces one of the greatest challenges in the field of health care. The main goal of this discipline is to ensure that patients treated for cancer do not suffer or die from cardiovascular disease. The number of studies on the mechanisms
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Cardio-oncology currently faces one of the greatest challenges in the field of health care. The main goal of this discipline is to ensure that patients treated for cancer do not suffer or die from cardiovascular disease. The number of studies on the mechanisms of heart injury during cancer treatment is constantly increasing. However, there is insufficient data on heart rhythm disorders that may result from this treatment. This issue seems to be particularly important in patients with lung cancer, in whom anticancer therapy, especially radiotherapy, may contribute to the onset of cardiac arrhythmias. The observed relationship between cardiac dosimetry and radiotherapy-induced cardiotoxicity in lung cancer treatment may explain the increased mortality from cardiovascular causes in patients after chest irradiation. Further research is essential to elucidate the role of cardiac arrhythmias in this context. Conversely, recent reports have highlighted the application of stereotactic arrhythmia radioablation (STAR) in the treatment of ventricular tachycardia. This review of available studies on the epidemiology, pathogenesis, diagnosis, and treatment of arrhythmias in patients treated for lung cancer aims to draw attention to the need for regular cardiological monitoring in this group of patients. Improving cardiac care for patients with lung cancer has the potential to enhance their overall therapeutic outcomes.
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(This article belongs to the Special Issue Side Effects of Anticancer Therapy: Prevention and Management)
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Proton Reirradiation for High-Risk Recurrent or New Primary Breast Cancer
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, , , , , and
Cancers 2023, 15(24), 5722; https://doi.org/10.3390/cancers15245722 - 06 Dec 2023
Abstract
Radiotherapy is an integral component of multidisciplinary breast cancer care. Given how commonly radiotherapy is used in the treatment of breast cancer, many patients with recurrences have received previous radiotherapy. Patients with new primary breast cancer may also have received previous radiotherapy to
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Radiotherapy is an integral component of multidisciplinary breast cancer care. Given how commonly radiotherapy is used in the treatment of breast cancer, many patients with recurrences have received previous radiotherapy. Patients with new primary breast cancer may also have received previous radiotherapy to the thoracic region. Curative doses and comprehensive field photon reirradiation (reRT) have often been avoided in these patients due to concerns for severe toxicities to organs-at-risk (OARs), such as the heart, lungs, brachial plexus, and soft tissue. However, many patients may benefit from definitive-intent reRT, such as patients with high-risk disease features such as lymph node involvement and dermal/epidermal invasion. Proton therapy is a potentially advantageous treatment option for delivery of reRT due to its lack of exit dose and greater conformality that allow for enhanced non-target tissue sparing of previously irradiated tissues. In this review, we discuss the clinical applications of proton therapy for patients with breast cancer requiring reRT, the currently available literature and how it compares to historical photon reRT outcomes, treatment planning considerations, and questions in this area warranting further study. Given the dosimetric advantages of protons and the data reported to date, proton therapy is a promising option for patients who would benefit from the added locoregional disease control provided by reRT for recurrent or new primary breast cancer.
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(This article belongs to the Special Issue Current Progress in Proton Radiotherapy of Cancer)
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The Genomic Landscape of Urothelial Carcinoma with High and Low ERBB2 Expression
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, , , , , , , , , , , , and
Cancers 2023, 15(24), 5721; https://doi.org/10.3390/cancers15245721 - 06 Dec 2023
Abstract
Background: Recent data suggests that HER2-targeted treatment is efficacious in urothelial carcinoma (UC). We investigated the genomic, transcriptomic, and immune landscapes and clinical outcomes in UC segmented by ERBB2 expression. Methods: NextGen DNA/RNA sequencing was performed for 4743 UC tumors. A total of
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Background: Recent data suggests that HER2-targeted treatment is efficacious in urothelial carcinoma (UC). We investigated the genomic, transcriptomic, and immune landscapes and clinical outcomes in UC segmented by ERBB2 expression. Methods: NextGen DNA/RNA sequencing was performed for 4743 UC tumors. A total of 3% (124/4125) of tumors had HER2 IHC and whole transcriptome sequencing (WTS) data. ERRB2-high and -low tumors were defined by ≥75th and <25th percentiles of ERBB2 expression, respectively. PD-L1 (SP142) positive staining was defined as ≥2+ and ≥5%. HER2 (4B5) positive staining was defined as ≥3+ and >10% or 2+ and >10% with positive HER2 in situ hybridization (ISH). Results: Of the patients who were ERBB2-high, 79% (61/77) were HER2 positive via IHC. Tumors from lower tract UC had higher ERBB2 expression compared to upper tract UC (50 v 40 median TPM (mTPM), p < 0.001). ERBB2 expression was similar between primary and metastatic tumors (47 v 47 mTPM, p = 0.95). ERBB2-high tumors had a higher prevalence of pathogenic mutations in pTERT, ERBB2, and ELF3 versus ERBB2-low tumors, p < 0.001. ERBB2-high tumors had higher expressions of ADC target genes NECTIN4 (12 v 8 mTPM) and TACSTD2 (366 v 74 mTPM) versus ERBB2-low (p < 0.001), as well as better overall survival from time of tissue sampling than ERBB2-low (HR 1.71, p < 0.001). Conclusion: Our study demonstrated a high concordance between HER2 expression by IHC and ERBB2 gene expression by WTS in UC. Differences in ADC target expression between ERBB2-high vs. ERBB2-low UC may provide a rationale for combination treatment strategies with HER2-ADC. The association between high ERBB2 expression and survival advantage warrants further investigation.
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(This article belongs to the Section Cancer Biomarkers)
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Practical Challenges of DBT-Guided VABB: Harms and Benefits, from Literature to Clinical Experience
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, , , and
Cancers 2023, 15(24), 5720; https://doi.org/10.3390/cancers15245720 - 06 Dec 2023
Abstract
Vacuum-assisted breast biopsy (VABB) guided by digital breast tomosynthesis (DBT) represents one of the best instruments to obtain a histological diagnosis of suspicious lesions with no ultrasound correlation or those which are visible only on DBT. After a review of the literature, we
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Vacuum-assisted breast biopsy (VABB) guided by digital breast tomosynthesis (DBT) represents one of the best instruments to obtain a histological diagnosis of suspicious lesions with no ultrasound correlation or those which are visible only on DBT. After a review of the literature, we retrospectively analyzed the DBT-guided VABBs performed from 2019 to 2022 at our department. Descriptive statistics, Pearson’s correlation and χ2 test were used to compare distributions of age, breast density (BD) and early performance measures including histopathology. We used kappa statistics to evaluate the agreement between histological assessment and diagnosis. Finally, we compared our experience to the literature to provide indications for clinical practice. We included 85 women aged 41–84 years old. We identified 37 breast cancers (BC), 26 stage 0 and 11 stage IA. 67.5% of BC was diagnosed in women with high BD. The agreement between VABB and surgery was 0.92 (k value, 95% CI: 0.76–1.08). We found a statistically significant inverse correlation between age and BD. The post-procedural clip was correctly positioned in 88.2%. The post-procedural hematoma rate was 14.1%. No infection or hemorrhage were recorded. When executed correctly, DBT-guided VABB represents a safe and minimally invasive technique with high histopathological concordance, for detecting nonpalpable lesions without ultrasound correlation.
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(This article belongs to the Special Issue Risk Factor Prediction, Diagnosis and Treatment of Breast Cancer)
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Androgen Receptor/AP-1 Activates UGT2B15 Transcription to Promote Esophageal Squamous Cell Carcinoma Invasion
Cancers 2023, 15(24), 5719; https://doi.org/10.3390/cancers15245719 - 06 Dec 2023
Abstract
Esophageal squamous cell carcinoma (ESCC) is an aggressive epithelial malignancy with poor prognosis. Interestingly, ESCC is strongly characterized by a male-predominant propensity. Our previous study showed that androgen receptor (AR) orchestrated a transcriptional repression program to promote ESCC growth, but it remains unclear
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Esophageal squamous cell carcinoma (ESCC) is an aggressive epithelial malignancy with poor prognosis. Interestingly, ESCC is strongly characterized by a male-predominant propensity. Our previous study showed that androgen receptor (AR) orchestrated a transcriptional repression program to promote ESCC growth, but it remains unclear whether AR can also activate oncogenic signaling during ESCC progression. In this study, by analyzing our previous AR cistromes and androgen-regulated transcriptomes, we identified uridine diphosphate glucuronosyltransferase family 2 member B15 (UGT2B15) as a bona fide target gene of AR. Mechanistically, AP-1 cofactors played important and collaborative roles in AR-mediated UGT2B15 upregulation. Functional studies have revealed that UGT2B15 promoted invasiveness in vitro and lymph node metastasis in vivo. UGT2B15 was partially responsible for the AR-induced invasive phenotype in ESCC cells. Importantly, simultaneous blocking of AP-1 and AR resulted in stronger inhibition of cell invasiveness compared to inhibiting AP-1 or AR alone. In conclusion, our study reveals the molecular mechanisms underlying the AR-driven ESCC invasion and suggests that the AR/AP1/UGT2B15 transcriptional axis can be potentially targeted in suppressing metastasis in male ESCC patients.
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(This article belongs to the Section Cancer Metastasis)
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Antitumor Activity of the Xanthonoside XGAc in Triple-Negative Breast, Ovarian and Pancreatic Cancer by Inhibiting DNA Repair
by
, , , , , , , and
Cancers 2023, 15(24), 5718; https://doi.org/10.3390/cancers15245718 - 06 Dec 2023
Abstract
Dysregulation of the DNA damage response may contribute to the sensitization of cancer cells to DNA-targeting agents by impelling cell death. In fact, the inhibition of the DNA repair pathway is considered a promising anticancer therapeutic strategy, particularly in combination with standard-of-care agents.
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Dysregulation of the DNA damage response may contribute to the sensitization of cancer cells to DNA-targeting agents by impelling cell death. In fact, the inhibition of the DNA repair pathway is considered a promising anticancer therapeutic strategy, particularly in combination with standard-of-care agents. The xanthonoside XGAc was previously described as a potent inhibitor of cancer cell growth. Herein, we explored its antitumor activity against triple-negative breast cancer (TNBC), ovarian cancer and pancreatic ductal adenocarcinoma (PDAC) cells as a single agent and in combination with the poly(ADP-ribose) polymerase inhibitor (PARPi) olaparib. We demonstrated that XGAc inhibited the growth of TNBC, ovarian and PDAC cells by inducing cell cycle arrest and apoptosis. XGAc also induced genotoxicity, inhibiting the expression of DNA repair proteins particularly involved in homologous recombination, including BRCA1, BRCA2 and RAD51. Moreover, it displayed potent synergistic effects with olaparib in TNBC, ovarian cancer and PDAC cells. Importantly, this growth inhibitory activity of XGAc was further reinforced in a TNBC spheroid model and in patient-derived ovarian cancer cells. Also, drug-resistant cancer cells showed no cross-resistance to XGAc. Additionally, the ability of XGAc to prevent cancer cell migration was evidenced in TNBC, ovarian cancer and PDAC cells. Altogether, these results highlight the great potential of acetylated xanthonosides such as XGAc as promising anticancer agents against hard-to-treat cancers.
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(This article belongs to the Special Issue Genetics and Epigenetics of Gynecological Cancer)
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Plasma Markers for Therapy Response Monitoring in Patients with Neuroendocrine Tumors Undergoing Peptide Receptor Radionuclide Therapy
by
, , , , , , , and
Cancers 2023, 15(24), 5717; https://doi.org/10.3390/cancers15245717 - 06 Dec 2023
Abstract
Background: Pretherapeutic chromogranin A, alkaline phosphatase (ALP), or De Ritis ratio (aspartate aminotransferase/alanine aminotransferase) are prognostic factors in patients with metastatic neuroendocrine tumors (NET) undergoing peptide receptor radionuclide therapy (PRRT). However, their value for intratherapeutic monitoring remains unclear. We evaluated if changes in
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Background: Pretherapeutic chromogranin A, alkaline phosphatase (ALP), or De Ritis ratio (aspartate aminotransferase/alanine aminotransferase) are prognostic factors in patients with metastatic neuroendocrine tumors (NET) undergoing peptide receptor radionuclide therapy (PRRT). However, their value for intratherapeutic monitoring remains unclear. We evaluated if changes in plasma markers during PRRT can help identify patients with unfavorable outcomes. Methods: A monocentric retrospective analysis of 141 patients with NET undergoing PRRT with [177Lu]Lu-DOTATOC was conducted. Changes in laboratory parameters were calculated by dividing the values determined immediately before each cycle of PRRT by the pretherapeutic value. Patients with low vs. high PFS were compared with the Wilcoxon rank-sum test. Results: Progression, relapse, or death after PRRT was observed in 103/141 patients. Patients with low PFS showed a significant relative ALP increase before the third (p = 0.014) and fourth (p = 0.039) cycles of PRRT. Kaplan–Meier analysis revealed a median PFS of 24.3 months (95% CI, 20.7–27.8 months) in patients with decreasing ALP values (Δ > 10%) during treatment, 12.5 months (95% CI, 9.2–15.8 months) in patients with increasing ALP values (Δ > 10%), and 17.7 months (95% CI, 13.6–21.8 months) with stable ALP values (Δ ± 10%). Conclusions: Based on these exploratory data, a rise in plasma ALP might indicate disease progression and should be interpreted cautiously during therapy.
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(This article belongs to the Special Issue Oncology: State-of-the-Art Research in Germany)
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Open AccessReview
Clinical Next Generation Sequencing Application in Mesothelioma: Finding a Golden Needle in the Haystack
by
, , , , and
Cancers 2023, 15(24), 5716; https://doi.org/10.3390/cancers15245716 - 06 Dec 2023
Abstract
Mesothelioma comprises a group of rare cancers arising from the mesothelium of the pleura, peritoneum, tunica vaginalis testis and pericardium. Mesothelioma is generally associated with asbestos exposure and has a dismal prognosis, with few therapeutic options. Several next generation sequencing (NGS) experiments have
[...] Read more.
Mesothelioma comprises a group of rare cancers arising from the mesothelium of the pleura, peritoneum, tunica vaginalis testis and pericardium. Mesothelioma is generally associated with asbestos exposure and has a dismal prognosis, with few therapeutic options. Several next generation sequencing (NGS) experiments have been performed on mesothelioma arising at different sites. These studies highlight a genomic landscape mainly characterized by a high prevalence (>20%) of genomic aberrations leading to functional losses in oncosuppressor genes such as BAP1, CDKN2A, NF2, SETD2 and TP53. Nevertheless, to date, evidence of the effect of targeting these alterations with specific drugs is lacking. Conversely, 1–2% of mesothelioma might harbor activating mutations in oncogenes with specifically approved drugs. The goal of this review is to summarize NGS applications in mesothelioma and to provide insights into target therapy of mesothelioma guided by NGS.
Full article
(This article belongs to the Special Issue Advances in Malignant Pleural Mesothelioma (MPM))

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