Topic Editors

Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Messina, Italy
Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D’Alcontres, 31-98166 Messina, Italy
Dr. Marika Lanza
Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D’Alcontres, 31-98166 Messina, Italy
Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D’Alcontres, 31-98166 Messina, Italy

Novel Discoveries in Oncology

Abstract submission deadline
closed (20 September 2023)
Manuscript submission deadline
30 November 2024
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Topic Information

Dear Colleagues,

The close relationship between tumor progression and pharmacological resistance has prompted us to investigate new mechanisms of molecular signaling involved in supporting tumor growth and survival. Recent advances in the development of oncology inhibitors are providing novel approaches for combating cancer. This Topic aims to highlight the latest advances in novel, promising therapeutic approaches, targeting tumor biomarkers and molecular pathway at basic, translational, and clinical levels. The aim is to discuss the latest developments and explore new ideas and future directions. Original research papers and review articles are welcomed.

Dr. Alessia Filippone
Dr. Giovanna Casili
Dr. Marika Lanza
Dr. Michela Campolo
Topic Editors

Keywords

  • molecular pathway
  • tumorigenesis
  • target-therapy
  • nervous system tumors
  • gastro-intestinal tumors
  • cell death
  • angiogenesis
  • biomarkers
  • oxidative stress

Participating Journals

Journal Name Impact Factor CiteScore Launched Year First Decision (median) APC
Biomolecules
biomolecules
4.8 9.4 2011 16.3 Days CHF 2700 Submit
Cancers
cancers
4.5 8.0 2009 16.3 Days CHF 2900 Submit
Cells
cells
5.1 9.9 2012 17.5 Days CHF 2700 Submit
International Journal of Molecular Sciences
ijms
4.9 8.1 2000 18.1 Days CHF 2900 Submit
Journal of Clinical Medicine
jcm
3.0 5.7 2012 17.3 Days CHF 2600 Submit
Journal of Molecular Pathology
jmp
- - 2020 25.4 Days CHF 1000 Submit
Organoids
organoids
- - 2022 15.0 days * CHF 1000 Submit

* Median value for all MDPI journals in the first half of 2024.


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Published Papers (18 papers)

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19 pages, 3091 KiB  
Article
A Novel Pyrazole Exhibits Potent Anticancer Cytotoxicity via Apoptosis, Cell Cycle Arrest, and the Inhibition of Tubulin Polymerization in Triple-Negative Breast Cancer Cells
by Edgar A. Borrego, Cristina D. Guerena, Austre Y. Schiaffino Bustamante, Denisse A. Gutierrez, Carlos A. Valenzuela, Ana P. Betancourt, Armando Varela-Ramirez and Renato J. Aguilera
Cells 2024, 13(14), 1225; https://doi.org/10.3390/cells13141225 - 20 Jul 2024
Viewed by 1022
Abstract
In this study, we screened a chemical library to find potent anticancer compounds that are less cytotoxic to non-cancerous cells. This study revealed that pyrazole PTA-1 is a potent anticancer compound. Additionally, we sought to elucidate its mechanism of action (MOA) in triple-negative [...] Read more.
In this study, we screened a chemical library to find potent anticancer compounds that are less cytotoxic to non-cancerous cells. This study revealed that pyrazole PTA-1 is a potent anticancer compound. Additionally, we sought to elucidate its mechanism of action (MOA) in triple-negative breast cancer cells. Cytotoxicity was analyzed with the differential nuclear staining assay (DNS). Additional secondary assays were performed to determine the MOA of the compound. The potential MOA of PTA-1 was assessed using whole RNA sequencing, Connectivity Map (CMap) analysis, in silico docking, confocal microscopy, and biochemical assays. PTA-1 is cytotoxic at a low micromolar range in 17 human cancer cell lines, demonstrating less cytotoxicity to non-cancerous human cells, indicating a favorable selective cytotoxicity index (SCI) for the killing of cancer cells. PTA-1 induced phosphatidylserine externalization, caspase-3/7 activation, and DNA fragmentation in triple-negative breast MDA-MB-231 cells, indicating that it induces apoptosis. Additionally, PTA-1 arrests cells in the S and G2/M phases. Furthermore, gene expression analysis revealed that PTA-1 altered the expression of 730 genes at 24 h (198 upregulated and 532 downregulated). A comparison of these gene signatures with those within CMap indicated a profile similar to that of tubulin inhibitors. Subsequent studies revealed that PTA-1 disrupts microtubule organization and inhibits tubulin polymerization. Our results suggest that PTA-1 is a potent drug with cytotoxicity to various cancer cells, induces apoptosis and cell cycle arrest, and inhibits tubulin polymerization, indicating that PTA-1 is an attractive drug for future clinical cancer treatment. Full article
(This article belongs to the Topic Novel Discoveries in Oncology)
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13 pages, 2451 KiB  
Article
Comparative Assessment of miR-185-5p and miR-191-5p Expression: From Normal Endometrium to High-Grade Endometrial Cancer
by Sergio Antonio Oropeza-de Lara, Idalia Garza-Veloz, Bertha Berthaud-González, Tania Guillermina Tirado-Navarro, Reinaldo Gurrola-Carlos, Bernardo Bonilla-Rocha, Ivan Delgado-Enciso and Margarita L. Martinez-Fierro
Cells 2024, 13(13), 1099; https://doi.org/10.3390/cells13131099 - 25 Jun 2024
Viewed by 1431
Abstract
Endometrial cancer (EC) is a significant cause of cancer-related deaths in women. MicroRNAs (miRs) play a role in cancer development, acting as oncogenes or tumor suppressors. This study evaluated the diagnostic potential of hsa-miR-185-5p and hsa-miR-191-5p in EC and their correlation with clinical [...] Read more.
Endometrial cancer (EC) is a significant cause of cancer-related deaths in women. MicroRNAs (miRs) play a role in cancer development, acting as oncogenes or tumor suppressors. This study evaluated the diagnostic potential of hsa-miR-185-5p and hsa-miR-191-5p in EC and their correlation with clinical and histopathological features. A cross-sectional study analyzed formalin-fixed, paraffin-embedded tissue samples from 59 patients: 18 with EC, 21 with endometrial hyperplasia (EH), 17 with normal endometrium (NE), and 3 with endometrial polyps (EPs). Quantitative reverse transcription-polymerase chain reaction and TaqMan probes were used for miR expression analysis. The Shapiro–Wilk test was used to analyze the normal distribution of the data. Subsequently, parametric or non-parametric tests were used to evaluate the associations between the expression levels of each miR and clinical parameters. Both miRs were underexpressed in some precursor and malignant lesions compared to certain NE subtypes and benign lesions. Specifically, hsa-miR-185-5p showed underexpression in grade 3 EC compared to some NE and EH subtypes (FC: −57.9 to −8.5, p < 0.05), and hsa-miR-191-5p was underexpressed in EH and EC compared to secretory endometrium and EPs (FC: −4.2 to −32.8, p < 0.05). SETD1B, TJP1, and MSI1 were common predicted target genes. In conclusion, hsa-miR-185-5p and hsa-miR-191-5p are underexpressed in EC tissues, correlating with histopathological grades, highlighting their potential as diagnostic biomarkers and their role as tumor suppressors in EC. Full article
(This article belongs to the Topic Novel Discoveries in Oncology)
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11 pages, 2269 KiB  
Article
Bilateral Uveal Melanoma: An Insight into Genetic Predisposition in Four New Unrelated Patients and Review of Published Cases
by Paula Silva-Rodríguez, Manuel Bande, María Pardo, Fernando Domínguez, Lourdes Loidi and María José Blanco-Teijeiro
J. Clin. Med. 2024, 13(11), 3035; https://doi.org/10.3390/jcm13113035 - 22 May 2024
Viewed by 672
Abstract
Background: Primary bilateral uveal melanoma (BUM) is an exceptionally rare form of uveal melanoma (UM). This study aimed to explore the potential existence of a genetic predisposition towards the development of BUM. Methods: We employed an exome sequencing approach on germline [...] Read more.
Background: Primary bilateral uveal melanoma (BUM) is an exceptionally rare form of uveal melanoma (UM). This study aimed to explore the potential existence of a genetic predisposition towards the development of BUM. Methods: We employed an exome sequencing approach on germline DNA from four unrelated patients diagnosed with BUM, seeking pathogenic or likely pathogenic variants indicative of a genetic predisposition to UM. Results: None of the patients exhibited pathogenic variants in the BAP1 gene. However, loss-of-function (LoF) variants in the TERF2IP and BAX genes were identified in two of the BUM patients. For patients BUM1 and BUM2, no pathogenic/likely pathogenic variants of significant clinical relevance to BUM were found to warrant inclusion in this report. Conclusions: Our findings suggest the presence of yet-to-be-discovered genes that may contribute to UM predisposition, as evidenced by the absence of pathogenic variants in known UM predisposition genes among the four BUM patients studied. The TERF2IP and BAX genes emerge as noteworthy candidates for further investigation regarding their role in genetic predisposition to UM. Specifically, the potential role of UM as a candidate cancer within the spectrum of cancers linked to pathogenic variants in the TERF2IP gene and other genes associated with the shelterin complex warrants further examination. Additional functional studies are necessary to support or challenge this hypothesis. Full article
(This article belongs to the Topic Novel Discoveries in Oncology)
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10 pages, 1790 KiB  
Article
Peritumor Mucosa in Advanced Laryngeal Carcinoma Exhibits an Aberrant Proangiogenic Signature Distinctive from the Expression Pattern in Adjacent Tumor Tissue
by Silva G. Kyurkchiyan, Gergana Stancheva, Veronika Petkova, Stiliana Panova, Venera Dobriyanova, Iglika Stancheva, Venelin Marinov, Zahari Zahariev, Radka P. Kaneva and Todor M. Popov
Cells 2024, 13(7), 633; https://doi.org/10.3390/cells13070633 - 5 Apr 2024
Viewed by 1172
Abstract
The field cancerization theory is an important paradigm in head and neck carcinoma as its oncological repercussions affect treatment outcomes in diverse ways. The aim of this study is to assess the possible interconnection between peritumor mucosa and the process of tumor neoangiogenesis. [...] Read more.
The field cancerization theory is an important paradigm in head and neck carcinoma as its oncological repercussions affect treatment outcomes in diverse ways. The aim of this study is to assess the possible interconnection between peritumor mucosa and the process of tumor neoangiogenesis. Sixty patients with advanced laryngeal carcinoma were enrolled in this study. The majority of patients express a canonical HIF-upregulated proangiogenic signature with almost complete predominancy of HIF-1α overexpression and normal expression levels of the HIF-2α isoform. Remarkably, more than 60% of the whole cohort also exhibited an HIF-upregulated proangiogenic signature in the peritumoral benign mucosa. Additionally, the latter subgroup had a distinctly shifted phenotype towards HIF-2α upregulation compared to the one in tumor tissue, i.e., a tendency towards an HIF switch is observed in contrast to the dominated by HIF-1α tumor phenotype. ETS-1 displays stable and identical significant overexpression in both the proangiogenic phenotypes present in tumor and peritumoral mucosa. In the current study, we report for the first time the existence of an abnormal proangiogenic expression profile present in the peritumoral mucosa in advanced laryngeal carcinoma when compared to paired distant laryngeal mucosa. Moreover, we describe a specific phenotype of this proangiogenic signature that is significantly different from the one present in tumor tissue as we delineate both phenotypes, quantitively and qualitatively. This finding is cancer heterogeneity, per se, which extends beyond the “classical” borders of the malignancy, and it is proof of a strong interconnection between field cancerization and one of the classical hallmarks of cancer—the process of tumor neoangiogenesis. Full article
(This article belongs to the Topic Novel Discoveries in Oncology)
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15 pages, 934 KiB  
Article
Clinical Benefit from Docetaxel +/− Ramucirumab Is Not Associated with Mutation Status in Metastatic Non-Small-Cell Lung Cancer Patients Who Progressed on Platinum Doublets and Immunotherapy
by Kang Qin, Kaiwen Wang, Shenduo Li, Lingzhi Hong, Priyadharshini Padmakumar, Rinsurongkawong Waree, Shawna M. Hubert, Xiuning Le, Natalie Vokes, Kunal Rai, Ara Vaporciyan, Don L. Gibbons, John V. Heymach, J. Jack Lee, Scott E. Woodman, Caroline Chung, David A. Jaffray, Mehmet Altan, Yanyan Lou and Jianjun Zhang
Cancers 2024, 16(5), 935; https://doi.org/10.3390/cancers16050935 - 26 Feb 2024
Cited by 1 | Viewed by 1692
Abstract
Docetaxel +/− ramucirumab remains the standard-of-care therapy for patients with metastatic non-small-cell lung cancer (NSCLC) after progression on platinum doublets and immune checkpoint inhibitors (ICIs). The aim of our study was to investigate whether the cancer gene mutation status was associated with clinical [...] Read more.
Docetaxel +/− ramucirumab remains the standard-of-care therapy for patients with metastatic non-small-cell lung cancer (NSCLC) after progression on platinum doublets and immune checkpoint inhibitors (ICIs). The aim of our study was to investigate whether the cancer gene mutation status was associated with clinical benefits from docetaxel +/− ramucirumab. We also investigated whether platinum/taxane-based regimens offered a better clinical benefit in this patient population. A total of 454 patients were analyzed (docetaxel +/− ramucirumab n=381; platinum/taxane-based regimens n=73). Progression-free survival (PFS) and overall survival (OS) were compared among different subpopulations with different cancer gene mutations and between patients who received docetaxel +/− ramucirumab versus platinum/taxane-based regimens. Among patients who received docetaxel +/− ramucirumab, the top mutated cancer genes included TP53 (n=167), KRAS (n=127), EGFR (n=65), STK11 (n=32), ERBB2 (HER2) (n=26), etc. None of these cancer gene mutations or PD-L1 expression was associated with PFS or OS. Platinum/taxane-based regimens were associated with a significantly longer mQS (13.00 m, 95% Cl: 11.20–14.80 m versus 8.40 m, 95% Cl: 7.12–9.68 m, LogRank P=0.019) than docetaxel +/− ramcirumab. Key prognostic factors including age, histology, and performance status were not different between these two groups. In conclusion, in patients with metastatic NSCLC who have progressed on platinum doublets and ICIs, the clinical benefit from docetaxel +/− ramucirumab is not associated with the cancer gene mutation status. Platinum/taxane-based regimens may offer a superior clinical benefit over docetaxel +/− ramucirumab in this patient population. Full article
(This article belongs to the Topic Novel Discoveries in Oncology)
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18 pages, 1573 KiB  
Review
Zinc Finger and BTB Domain-Containing 20: A Newly Emerging Player in Pathogenesis and Development of Human Cancers
by Jiangyuan Liu and Han Zhang
Biomolecules 2024, 14(2), 192; https://doi.org/10.3390/biom14020192 - 4 Feb 2024
Viewed by 1814
Abstract
Zinc finger and BTB domain-containing 20 (ZBTB20), which was initially identified in human dendritic cells, belongs to a family of transcription factors (TFs) with an N-terminal BTB domain and one or more C-terminal DNA-binding zinc finger domains. Under physiological conditions, ZBTB20 acts as [...] Read more.
Zinc finger and BTB domain-containing 20 (ZBTB20), which was initially identified in human dendritic cells, belongs to a family of transcription factors (TFs) with an N-terminal BTB domain and one or more C-terminal DNA-binding zinc finger domains. Under physiological conditions, ZBTB20 acts as a transcriptional repressor in cellular development and differentiation, metabolism, and innate immunity. Interestingly, multiple lines of evidence from mice and human systems have revealed the importance of ZBTB20 in the pathogenesis and development of cancers. ZBTB20 is not only a hotspot of genetic variation or fusion in many types of human cancers, but also a key TF or intermediator involving in the dysregulation of cancer cells. Given the diverse functions of ZBTB20 in both health and disease, we herein summarize the structure and physiological roles of ZBTB20, with an emphasis on the latest findings on tumorigenesis and cancer progression. Full article
(This article belongs to the Topic Novel Discoveries in Oncology)
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10 pages, 220 KiB  
Article
Effect of Selective 5-Hydroxytryptamine-3 Receptor and Neurokinin-1 Receptor Antagonists on Hemodynamic Changes and Arrhythmogenic Potential in Patients Receiving Chemotherapy: A Retrospective, Observational Study
by Utku Burak Bozbulut, Tuğba Cengiz and Ahmet Özet
J. Clin. Med. 2024, 13(3), 843; https://doi.org/10.3390/jcm13030843 - 1 Feb 2024
Viewed by 755
Abstract
Background: Prior speculation suggests that selective 5-hydroxytryptamine-3 receptors and neurokinin-1 receptor antagonists may increase arrhythmia risk and induce electrocardiographic changes. This study examined the effect of anti-emetic medications on arrhythmogenic potential and hemodynamic alterations. Methods: We considered patients aged 18 or above receiving [...] Read more.
Background: Prior speculation suggests that selective 5-hydroxytryptamine-3 receptors and neurokinin-1 receptor antagonists may increase arrhythmia risk and induce electrocardiographic changes. This study examined the effect of anti-emetic medications on arrhythmogenic potential and hemodynamic alterations. Methods: We considered patients aged 18 or above receiving chemotherapy between June 2013 and December 2013. Patients were grouped by anti-emetic medication: intravenous granisetron (Group G), oral aprepitant plus IV granisetron (Group AG), IV palonosetron (Group P), and oral aprepitant plus IV palonosetron (Group AP). We recorded blood pressure and electrocardiography initially and at the thirtieth minute post-medication, focusing on P dispersion, QTc dispersion, and systolic/diastolic blood pressure alterations. Results: The study included 80 patients (20 per group). Baseline systolic/diastolic blood pressure and P dispersion showed no significant variance. However, the baseline QTc dispersion was significantly lower in Groups P and AP than G and AG. The thirtieth-minute systolic/diastolic blood pressures were significantly lower than the baseline for Groups AG and AP, and the heart rates decreased in all groups. Group P showed significantly fewer blood pressure changes. Conclusions: We found no arrhythmogenic potential linked to granisetron, palonosetron, and aprepitant. Hypotension was more frequent at 30 min post-medication in granisetron or aprepitant recipients. Considering no hypotension occurred when using palonosetron alone, this treatment was deemed safer. Full article
(This article belongs to the Topic Novel Discoveries in Oncology)
14 pages, 877 KiB  
Review
The Biological and Clinical Role of the Telomerase Reverse Transcriptase Gene in Glioblastoma: A Potential Therapeutic Target?
by Vincenzo Di Nunno, Marta Aprile, Stefania Bartolini, Lidia Gatto, Alicia Tosoni, Lucia Ranieri, Dario De Biase, Sofia Asioli and Enrico Franceschi
Cells 2024, 13(1), 44; https://doi.org/10.3390/cells13010044 - 25 Dec 2023
Cited by 2 | Viewed by 1793
Abstract
Glioblastoma IDH-wildtype represents the most lethal and frequent primary tumor of the central nervous system. Thanks to important scientific efforts, we can now investigate its deep genomic assessment, elucidating mutated genes and altered biological mechanisms in addition to its clinical aggressiveness. The [...] Read more.
Glioblastoma IDH-wildtype represents the most lethal and frequent primary tumor of the central nervous system. Thanks to important scientific efforts, we can now investigate its deep genomic assessment, elucidating mutated genes and altered biological mechanisms in addition to its clinical aggressiveness. The telomerase reverse transcriptase gene (TERT) is the most frequently altered gene in solid tumors, including brain tumors and GBM IDH-wildtype. In particular, it can be observed in approximately 80–90% of GBM IDH-wildtype cases. Its clonal distribution on almost all cancer cells makes this gene an optimal target. However, the research of effective TERT inhibitors is complicated by several biological and clinical obstacles which can be only partially surmounted. Very recently, novel immunological approaches leading to TERT inhibition have been investigated, offering the potential to develop an effective target for this altered protein. Here, we perform a narrative review investigating the biological role of TERT alterations on glioblastoma and the principal obstacles associated with TERT inhibitions in this population. Moreover, we discuss possible combination treatment strategies to overcome these limitations. Full article
(This article belongs to the Topic Novel Discoveries in Oncology)
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14 pages, 2970 KiB  
Article
Exploring the Safety of Pllans-II and Antitumoral Potential of Its Recombinant Isoform in Cervical Cancer Therapy
by María José Sevilla-Sánchez, Alejandro Montoya-Gómez, Daniel Osorno-Valencia, Leonel Montealegre-Sánchez, Mildrey Mosquera-Escudero and Eliécer Jiménez-Charris
Cells 2023, 12(24), 2812; https://doi.org/10.3390/cells12242812 - 10 Dec 2023
Cited by 1 | Viewed by 1267
Abstract
The antitumor potential of proteins from snake venoms has been studied in recent decades, and evidence has emerged that phospholipases A2 can selectively attack cells of various types of tumors. Previous results have shown that phospholipase A2Pllans-II, [...] Read more.
The antitumor potential of proteins from snake venoms has been studied in recent decades, and evidence has emerged that phospholipases A2 can selectively attack cells of various types of tumors. Previous results have shown that phospholipase A2Pllans-II, isolated from Porthidium lansbergii lansbergii snake venom, displayed antitumoral activity on cervical cancer and did not alter the viability of non-tumorigenic cells. However, until now, there was no evidence of its safety at the local and systemic levels, nor had experiments been developed to demonstrate that its production using recombinant technology allows us to obtain a molecule with effects similar to those generated by native phospholipase. Thus, we evaluated the impact caused by Pllans-II on murine biomodels, determining whether it induced local hemorrhage or increased pro-inflammatory and liver damage markers and histological alterations in the liver and kidneys. Additionally, the protein was produced using recombinant technology using a pET28a expression vector and the BL21 (DE3) Escherichia coli strain. Equally, its enzymatic activity and anticancer effect were evaluated on cervical cancer lines such as HeLa and Ca Ski. The results demonstrated that Pllans-II did not generate hemorrhagic activity, nor did it increase the pro-inflammatory cytokines IL-6, IL-1B, or TNF-α at doses of 3.28, 1.64, and 0.82 mg/kg. There was also no evidence of organ damage, and only ALT and AST increased in mild levels at the two highest concentrations. Additionally, the recombinant version of Pllans-II showed conservation in its catalytic activity and the ability to generate death in HeLa and Ca Ski cells (42% and 23%, respectively). These results demonstrate the innocuity of Pllans-II at the lowest dose and constitute an advance in considering a molecule produced using recombinant technology a drug candidate for selective attacks against cervical cancer. Full article
(This article belongs to the Topic Novel Discoveries in Oncology)
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25 pages, 837 KiB  
Article
Mobilising Collaboration among Stakeholders to Optimise the Growing Potential of Data for Tackling Cancer
by Denis Horgan, Marc Van den Bulcke, Umberto Malapelle, Nicola Normanno, Ettore D. Capoluongo, Arsela Prelaj, Carmelo Rizzari, Aliki Stathopoulou, Jaya Singh, Marta Kozaric, France Dube, Manuel Ottaviano, Stefania Boccia, Gabriella Pravettoni, Ivana Cattaneo, Núria Malats, Reinhard Buettner, Karim Lekadir, Francesco de Lorenzo, Catherine Alix-Panabieres, Sara Badreh, Paul Hofman, Ruggero De Maria and Eric Solaryadd Show full author list remove Hide full author list
J. Mol. Pathol. 2023, 4(4), 234-258; https://doi.org/10.3390/jmp4040021 - 27 Oct 2023
Cited by 3 | Viewed by 1907
Abstract
Effective cancer diagnosis, treatment and control depend on interactions among numerous distinct factors, from technology to data to skills to sociology. But a crucial influence is the extent to which the health system takes account of the distinct perspectives of the many different [...] Read more.
Effective cancer diagnosis, treatment and control depend on interactions among numerous distinct factors, from technology to data to skills to sociology. But a crucial influence is the extent to which the health system takes account of the distinct perspectives of the many different groups of interdependent stakeholders concerned with cancer, including patients, practitioners and planners. This paper provides some elucidation as to how far and how efficiently these interactions currently take place in Europe. It also makes some tentative suggestions as to how conscious systematic interventions could improve cancer outcomes. It is based on a series of expert panels and surveys conducted by the European Alliance for Personalised Medicine (EAPM) that provided information at the national level on three selected parameters: implementation of next-generation sequencing (NGS) and liquid biopsy (LB), attitudes of patients to prevention and practices of sharing genomic data among healthcare professionals (HCPs). The varying data infrastructure highlights the urgent need for substantial improvements to accommodate the increasing importance of genomics data in cancer diagnosis and care. Additionally, we identify disparities in age-specific approaches to cancer prevention, emphasising the necessity for tailored strategies to address unique age group perspectives. Moreover, distinct regional prioritizations in cancer treatment underscore the importance of considering regional variations when shaping future cancer care strategies. This study advocates for collaborative data sharing supported by technological innovation to overcome these challenges, ultimately fostering a holistic and equitable provision of cancer care in Europe. Full article
(This article belongs to the Topic Novel Discoveries in Oncology)
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29 pages, 34244 KiB  
Article
Prognostic, Immunological, and Mutational Analysis of MTA2 in Pan-Cancer and Drug Screening for Hepatocellular Carcinoma
by Xueshan Huang, Jingyi Tan, Mei Chen, Weirang Zheng, Shanyang Zou, Xiaoxia Ye, Yutong Li and Minhua Wu
Biomolecules 2023, 13(6), 883; https://doi.org/10.3390/biom13060883 - 24 May 2023
Cited by 2 | Viewed by 3600
Abstract
Background: Metastasis-associated protein 2 (MTA2) is a member of the metastasis-associated transcriptional regulator family and is a core component of the nucleosome remodeling and histone deacetylation complex. Despite growing evidence that MTA2 plays a crucial role in the tumorigenesis of certain cancers, no [...] Read more.
Background: Metastasis-associated protein 2 (MTA2) is a member of the metastasis-associated transcriptional regulator family and is a core component of the nucleosome remodeling and histone deacetylation complex. Despite growing evidence that MTA2 plays a crucial role in the tumorigenesis of certain cancers, no systematic pan-cancer analysis of MTA2 is available to date. Therefore, the aim of our study is to explore the prognostic value of MTA2 in 33 cancer types and to investigate its potential immune function. Methods: by comprehensive use of databases from TCGA, GTEx, GEO, UCSC xena, cBioPortal, comPPI, GeneMANIA, TCIA, MSigDB, and PDB, we applied various bioinformatics approaches to investigate the potential role of MTA2, including analyzing the association of MTA2 with MSI, prognosis, gene mutation, and immune cell infiltration in different tumors. We constructed a nomogram in TCGA-LIHC, performed single-cell sequencing (scRNA-seq) analysis of MTA2 in hepatocellular carcinoma (HCC), and screened drugs for the treatment of HCC. Finally, immunohistochemical experiments were performed to verify the expression and prognostic value of MTA2 in HCC. In vitro experiments were employed to observe the growth inhibition effects of MK-886 on the HCC cell line HepG2. Results: The results suggested that MTA2 was highly expressed in most cancers, and MTA2 expression was associated with the prognosis of different cancers. In addition, MTA2 expression was associated with Tumor Mutation Burden (TMB) in 12 cancer types and MSI in 8 cancer types. Immunoassays indicated that MTA2 positively correlated with activated memory CD4 T cells and M0 macrophage infiltration levels in HCC. ScRNA-seq analysis based on the GEO dataset discovered that MTA2 was significantly expressed in T cells in HCC. Finally, the eXtreme Sum (Xsum) algorithm was used to screen the antitumor drug MK-886, and the molecular docking technique was utilized to reveal the binding capacity between MK-886 and the MTA2 protein. The results demonstrated excellent binding sites between them, which bind to each other through Π-alkyl and alkyl interaction forces. An immunohistochemistry experiment showed that MTA2 protein was highly expressed in HCC, and high MTA2 expression was associated with poor survival in HCC patients. MK-886 significantly inhibited the proliferation and induced cell death of HepG2 cells in a dose-dependent manner. Conclusions: Our study demonstrated that MTA2 plays crucial roles in tumor progression and tumor immunity, and it could be used as a prognostic marker for various malignancies. MK-886 might be a powerful drug for HCC. Full article
(This article belongs to the Topic Novel Discoveries in Oncology)
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18 pages, 2593 KiB  
Review
Implications of the Organ-Specific Immune Environment for Immune Priming Effect of Radiotherapy in Metastatic Setting
by Julien Pierrard, Geneviève Van Ooteghem and Marc Van den Eynde
Biomolecules 2023, 13(4), 689; https://doi.org/10.3390/biom13040689 - 18 Apr 2023
Cited by 1 | Viewed by 1509
Abstract
With the development of immune checkpoint inhibitors (ICIs), the tumour immune microenvironment (TIME) has been increasingly considered to improve cancer management. The TIME of metastatic lesions is strongly influenced by the underlying immune contexture of the organ in which they are located. The [...] Read more.
With the development of immune checkpoint inhibitors (ICIs), the tumour immune microenvironment (TIME) has been increasingly considered to improve cancer management. The TIME of metastatic lesions is strongly influenced by the underlying immune contexture of the organ in which they are located. The metastatic location itself appears to be an important prognostic factor in predicting outcomes after ICI treatment in cancer patients. Patients with liver metastases are less likely to respond to ICIs than patients with metastases in other organs, likely due to variations in the metastatic TIME. Combining additional treatment modalities is an option to overcome this resistance. Radiotherapy (RT) and ICIs have been investigated together as an option to treat various metastatic cancers. RT can induce a local and systemic immune reaction, which can promote the patient’s response to ICIs. Here, we review the differential impact of the TIME according to metastatic location. We also explore how RT-induced TIME modifications could be modulated to improve outcomes of RT-ICI combinations. Full article
(This article belongs to the Topic Novel Discoveries in Oncology)
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10 pages, 1025 KiB  
Article
S100 as Serum Tumor Marker in Advanced Uveal Melanoma
by Martin Salzmann, Alexander H. Enk and Jessica C. Hassel
Biomolecules 2023, 13(3), 529; https://doi.org/10.3390/biom13030529 - 14 Mar 2023
Cited by 4 | Viewed by 4172
Abstract
S100 protein is routinely used as a serum tumor marker in advanced cutaneous melanoma. However, there is scarce and inconclusive evidence on its value in monitoring disease progression of uveal melanoma. In this monocenter study, we retrospectively assessed the connection between documented S100 [...] Read more.
S100 protein is routinely used as a serum tumor marker in advanced cutaneous melanoma. However, there is scarce and inconclusive evidence on its value in monitoring disease progression of uveal melanoma. In this monocenter study, we retrospectively assessed the connection between documented S100 protein levels of patients suffering from stage IV uveal melanoma and the clinical course of disease. Where available, we analyzed expression of S100 in melanoma metastases by immunohistochemistry. A total of 101 patients were included, 98 had available serum S100 levels, and in 83 cases, sufficient data were available to assess a potential link of S100 with the clinical course of the uveal melanoma. Only 12 of 58 (20.7%) patients had elevated serum levels at first diagnosis of stage IV disease. During progressive disease, 54% of patients showed rising serum S100 levels, while 46% of patients did not. Tumor material of 56 patients was stained for S100. Here, 26 (46.4%) showed expression, 19 (33.9%) weak expression, and 11 (19.6%) no expression of S100. Serum S100 levels rose invariably in all patients with strong expression throughout the course of disease, while patients without S100 expression in metastases never showed rising S100 levels. Thus, the value of S100 serum levels in monitoring disease progression can be predicted by immunohistochemistry of metastases. It is not a reliable marker for early detection of advanced disease. Full article
(This article belongs to the Topic Novel Discoveries in Oncology)
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18 pages, 2148 KiB  
Article
Soluble Guanylate Cyclase β1 Subunit Represses Human Glioblastoma Growth
by Haijie Xiao, Haifeng Zhu, Oliver Bögler, Fabiola Zakia Mónica, Alexander Y. Kots, Ferid Murad and Ka Bian
Cancers 2023, 15(5), 1567; https://doi.org/10.3390/cancers15051567 - 2 Mar 2023
Cited by 2 | Viewed by 1735
Abstract
Malignant glioma is the most common and deadly brain tumor. A marked reduction in the levels of sGC (soluble guanylyl cyclase) transcript in the human glioma specimens has been revealed in our previous studies. In the present study, restoring the expression of sGCβ1 [...] Read more.
Malignant glioma is the most common and deadly brain tumor. A marked reduction in the levels of sGC (soluble guanylyl cyclase) transcript in the human glioma specimens has been revealed in our previous studies. In the present study, restoring the expression of sGCβ1 alone repressed the aggressive course of glioma. The antitumor effect of sGCβ1 was not associated with enzymatic activity of sGC since overexpression of sGCβ1 alone did not influence the level of cyclic GMP. Additionally, sGCβ1-induced inhibition of the growth of glioma cells was not influenced by treatment with sGC stimulators or inhibitors. The present study is the first to reveal that sGCβ1 migrated into the nucleus and interacted with the promoter of the TP53 gene. Transcriptional responses induced by sGCβ1 caused the G0 cell cycle arrest of glioblastoma cells and inhibition of tumor aggressiveness. sGCβ1 overexpression impacted signaling in glioblastoma multiforme, including the promotion of nuclear accumulation of p53, a marked reduction in CDK6, and a significant decrease in integrin α6. These anticancer targets of sGCβ1 may represent clinically important regulatory pathways that contribute to the development of a therapeutic strategy for cancer treatment. Full article
(This article belongs to the Topic Novel Discoveries in Oncology)
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14 pages, 983 KiB  
Review
Critical Roles of METTL3 in Translation Regulation of Cancer
by Wangyang Meng, Han Xiao, Peiyuan Mei, Jiaping Chen, Yangwei Wang, Rong Zhao and Yongde Liao
Biomolecules 2023, 13(2), 243; https://doi.org/10.3390/biom13020243 - 27 Jan 2023
Cited by 6 | Viewed by 2739
Abstract
Aberrant translation, a characteristic feature of cancer, is regulated by the complex and sophisticated RNA binding proteins (RBPs) in the canonical translation machinery. N6-methyladenosine (m6A) modifications are the most abundant internal modifications in mRNAs mediated by methyltransferase-like 3 (METTL3). METTL3 is [...] Read more.
Aberrant translation, a characteristic feature of cancer, is regulated by the complex and sophisticated RNA binding proteins (RBPs) in the canonical translation machinery. N6-methyladenosine (m6A) modifications are the most abundant internal modifications in mRNAs mediated by methyltransferase-like 3 (METTL3). METTL3 is commonly aberrantly expressed in different tumors and affects the mRNA translation of many oncogenes or dysregulated tumor suppressor genes in a variety of ways. In this review, we discuss the critical roles of METTL3 in translation regulation and how METTL3 and m6A reader proteins in collaboration with RBPs within the canonical translation machinery promote aberrant translation in tumorigenesis, providing an overview of recent efforts aiming to ‘translate’ these results to the clinic. Full article
(This article belongs to the Topic Novel Discoveries in Oncology)
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13 pages, 5591 KiB  
Case Report
Chinese Pedigree with Hereditary Gastrointestinal Stromal Tumors: A Case Report and Literature Review
by Qichao Ge, Yang Liu, Fan Yang, Guangwei Sun, Jintao Guo and Siyu Sun
Int. J. Mol. Sci. 2023, 24(1), 830; https://doi.org/10.3390/ijms24010830 - 3 Jan 2023
Cited by 3 | Viewed by 2249
Abstract
Familial gastrointestinal stromal tumor (GIST) is a rare autosomal dominant genetic disorder with only a few affected families reported to date. Here, we report a case of familial GISTs harboring a novel germline mutation within exon 18 of KIT. A 58-year-old male [...] Read more.
Familial gastrointestinal stromal tumor (GIST) is a rare autosomal dominant genetic disorder with only a few affected families reported to date. Here, we report a case of familial GISTs harboring a novel germline mutation within exon 18 of KIT. A 58-year-old male patient presented with gastric subepithelial lesions accompanied by cutaneous hyperpigmentation, which were subsequently diagnosed as multinodular GISTs. Endoscopic surgery was initially conducted to remove the larger lesions, and pathological examinations were then conducted for the diagnosis of GISTs. Family history revealed that some other family members had similar cutaneous pigmentations. Whole-exome sequencing was used to search for potential driver mutations, and Sanger sequencing was used for mutation validation. A novel primary driver mutation of KIT (c.G2485C, p.A829P) was detected in these hereditary GISTs, which has been reported in some targeted chemotherapy-resistant GISTs. Cell models were subsequently established for the rapid screening of candidate drugs and exploring potential mechanisms. This mutation could lead to cell proliferation and imatinib resistance by ligand-independent activation of KIT; however, ripretinib administration was identified as an applicable targeted therapy for this mutation. The mutation activated the JAK/STAT3 and MAPK/ERK pathways, which could be inhibited by ripretinib administration. To the best of our knowledge, this is the first report of the KIT-A829P mutation in familial GISTs, complementing the pathogenesis of familial GISTs and providing valuable information for the precision treatment of this disease. Full article
(This article belongs to the Topic Novel Discoveries in Oncology)
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12 pages, 875 KiB  
Article
Prediagnosis Depression Rather Than Anxiety Symptoms Is Associated with Decreased Ovarian Cancer Survival: Findings from the Ovarian Cancer Follow-Up Study (OOPS)
by Yi-Zi Li, Xue Qin, Fang-Hua Liu, Wen-Xiao Chen, Yi-Fan Wei, Na Wang, Shi Yan, Ye Kang, Yu-Hong Zhao, Song Gao, Ting-Ting Gong and Qi-Jun Wu
J. Clin. Med. 2022, 11(24), 7394; https://doi.org/10.3390/jcm11247394 - 13 Dec 2022
Cited by 4 | Viewed by 1668
Abstract
Background: The relationship between prediagnosis depression, anxiety symptoms, and ovarian cancer (OC) survival is unknown. We aimed to explore these associations to provide further epidemiological evidence. Methods: We investigated the relationship between prediagnosis depression, anxiety symptoms, and OC survival in a prospective cohort [...] Read more.
Background: The relationship between prediagnosis depression, anxiety symptoms, and ovarian cancer (OC) survival is unknown. We aimed to explore these associations to provide further epidemiological evidence. Methods: We investigated the relationship between prediagnosis depression, anxiety symptoms, and OC survival in a prospective cohort study of newly diagnosed OC patients aged 18–79 years. Depression and anxiety symptoms were assessed using the Patient Health Questionnaire 9 and Generalized Anxiety Disorder 7 at diagnosis, respectively. Deaths were ascertained until 31 March 2021 via medical records and active follow-up. Multivariable-adjusted Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) with prediagnosis depression and anxiety symptoms and all-cause mortality of OC. Results: We found 56 (9.4%) and 235 (39.3%) OC patients with depression and anxiety symptoms, respectively. During a median follow-up of 37.2 months (interquartile range 24.7–50.2 months), 130 deaths were confirmed. Compared with non-depression symptoms, patients with prediagnosis depressive symptoms showed a significantly increased risk of OC mortality (HR = 2.10, 95% CI: 1.20–3.70). Of note, the association was still robust when focusing on the OC patients with severe depressive symptoms (HR = 2.10, 95% CI: 1.07–4.12). However, we observed no association between prediagnosis anxiety symptoms of different severity and OC mortality. Interestingly, OC patients with combined moderate depression and anxiety symptoms had a significantly increased risk of OC mortality (HR = 3.23, 95% CI: 1.14–9.11) compared to those with no symptoms of depression and anxiety. Notably, Wilms’s tumor 1 was significantly associated with depression and anxiety symptoms (p < 0.05). Conclusions: Prediagnosis depression increases the risk of OC mortality. Large multicenter studies are required to confirm this finding. Full article
(This article belongs to the Topic Novel Discoveries in Oncology)
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11 pages, 1616 KiB  
Article
CAR Triggered Release of Type-1 Interferon Limits CAR T-Cell Activities by an Artificial Negative Autocrine Loop
by Dennis Christoph Harrer, Charlotte Schenkel, Valerie Bezler, Marcell Kaljanac, Jordan Hartley, Markus Barden, Hong Pan, Astrid Holzinger, Wolfgang Herr and Hinrich Abken
Cells 2022, 11(23), 3839; https://doi.org/10.3390/cells11233839 - 30 Nov 2022
Cited by 6 | Viewed by 2656
Abstract
The advent of chimeric antigen receptor (CAR) T cells expedited the field of cancer immunotherapy enabling durable remissions in patients with refractory hematological malignancies. T cells redirected for universal cytokine-mediated killing (TRUCKs), commonly referred to as “fourth generation” CAR T-cells, are designed to [...] Read more.
The advent of chimeric antigen receptor (CAR) T cells expedited the field of cancer immunotherapy enabling durable remissions in patients with refractory hematological malignancies. T cells redirected for universal cytokine-mediated killing (TRUCKs), commonly referred to as “fourth generation” CAR T-cells, are designed to release engineered payloads upon CAR-induced T-cell activation. Building on the TRUCK technology, we aimed to generate CAR T-cells with a CAR-inducible artificial, self-limiting autocrine loop. To this end, we engineered CAR T-cells with CAR triggered secretion of type-1 interferons (IFNs). At baseline, IFNα and IFNβ CAR T-cells showed similar capacities in cytotoxicity and cytokine secretion compared to conventional CAR T-cells. However, under “stress” conditions of repetitive rounds of antigen stimulation using BxPC-3 pancreas carcinoma cells as targets, anti-tumor activity faded in later rounds while being fully active in destructing carcinoma cells during first rounds of stimulation. Mechanistically, the decline in activity was primarily based on type-1 IFN augmented CAR T-cell apoptosis, which was far less the case for CAR T-cells without IFN release. Such autocrine self-limiting loops can be used for applications where transient CAR T-cell activity and persistence upon target recognition is desired to avoid lasting toxicities. Full article
(This article belongs to the Topic Novel Discoveries in Oncology)
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