Special Issue "Genomic Instability in Tumor Evolution and Therapy Response"

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Pathophysiology".

Deadline for manuscript submissions: 1 May 2022.

Special Issue Editors

Dr. Ana María Zubiaga
E-Mail Website
Guest Editor
Dept. Genetics, Physical Anthropology and Animal Physiology, School of Science and Technology University of the Basque Country, Barrio Sarriena s/n, 48940 Leioa, Spain
Interests: RB/E2F pathway; cell cycle; transcriptional regulation; genomic stability; cell proliferation
Special Issues, Collections and Topics in MDPI journals
Dr. Jone Mitxelena
E-Mail Website
Guest Editor
Dept. Genetics, Physical Anthropology and Animal Physiology, School of Science and Technology University of the Basque Country, Barrio Sarriena s/n, 48940 Leioa, Spain
Interests: Cell cycle; Transcriptional regulation; Genomic stability; Replication stress

Special Issue Information

Dear Colleagues,

The integrity of the human genome is closely managed by an array of cell surveillance mechanisms, and its maintenance is essential for organism survival. To guarantee genomic integrity, cells have developed a highly sophisticated molecular network that ensures faithful DNA replication, repair of all types of DNA damage and accurate chromosome segregation in mitosis.

Genomic instability arises from perturbations involving failure to repair DNA damage, exogenous or endogenous genotoxic stress that overwhelms high-fidelity DNA replication and repair, oncogene-induced replication stress, chromothripsis, telomere dysfunction or defective mitosis, and it is presently considered a major driver of cancer development and progression. Moreover, persistent genome instability in tumors has been associated with their increased aggressive behavior and resistance to cancer therapies; consequently, it has prognostic and therapeutic significance.

This Special Issue is focused on studies that highlight recent advances in our understanding of genomic stability maintenance, from the drivers of instability to the cellular responses, as well as progress that is being made based on its exploitation as a vulnerability for cancer treatment. We cordially invite researchers working actively in these fields to submit their original research or review manuscripts to this Special Issue on genomic instability.

Dr. Ana María Zubiaga
Dr. Jone Mitxelena
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2400 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • genomic instability
  • DNA damage response
  • replication stress
  • oncogenic stress
  • transcription–replication conflicts
  • common fragile sites
  • telomere dysfunction
  • chromosome fragility
  • immune response to genome instability
  • precision therapy

Published Papers (3 papers)

Order results
Result details
Select all
Export citation of selected articles as:

Research

Jump to: Review

Article
Phospho-Ser784-VCP Drives Resistance of Pancreatic Ductal Adenocarcinoma to Genotoxic Chemotherapies and Predicts the Chemo-Sensitizing Effect of VCP Inhibitor
Cancers 2021, 13(20), 5076; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers13205076 - 11 Oct 2021
Viewed by 505
Abstract
Pancreatic ductal adenocarcinoma (PDAC) patients have a dismal prognosis due in large part to chemotherapy resistance. However, a small subset containing defects in the DNA damage response (DDR) pathways are chemotherapy-sensitive. Identifying intrinsic and therapeutically inducible DDR defects can improve precision and efficacy [...] Read more.
Pancreatic ductal adenocarcinoma (PDAC) patients have a dismal prognosis due in large part to chemotherapy resistance. However, a small subset containing defects in the DNA damage response (DDR) pathways are chemotherapy-sensitive. Identifying intrinsic and therapeutically inducible DDR defects can improve precision and efficacy of chemotherapies for PDAC. DNA repair requires dynamic reorganization of chromatin-associated proteins, which is orchestrated by the AAA+ ATPase VCP. We recently discovered that the DDR function of VCP is selectively activated by Ser784 phosphorylation. In this paper, we show that pSer784-VCP but not total VCP levels in primary PDAC tumors negatively correlate with patient survival. In PDAC cell lines, different pSer784-VCP levels are induced by genotoxic chemotherapy agents and positively correlate with genome stability and cell survival. Causal effects of pSer784-VCP on DNA repair and cell survival were confirmed using VCP knockdown and functional rescue. Importantly, DNA damage-induced pSer784-VCP rather than total VCP levels in PDAC cell lines predict their chemotherapy response and chemo-sensitizing ability of selective VCP inhibitor NMS-873. Therefore, pSer784-VCP drives genotoxic chemotherapy resistance of PDAC, and can potentially be used as a predictive biomarker as well as a sensitizing target to enhance the chemotherapy response of PDAC. Full article
(This article belongs to the Special Issue Genomic Instability in Tumor Evolution and Therapy Response)
Show Figures

Figure 1

Article
Copy Neutral LOH Affecting the Entire Chromosome 6 Is a Frequent Mechanism of HLA Class I Alterations in Cancer
Cancers 2021, 13(20), 5046; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers13205046 - 09 Oct 2021
Viewed by 415
Abstract
Total or partial loss of HLA class I antigens reduce the recognition of specific tumor peptides by cytotoxic T lymphocytes favoring cancer immune escape during natural tumor evolution. These alterations can be caused by genomic defects, such as loss of heterozygosity at chromosomes [...] Read more.
Total or partial loss of HLA class I antigens reduce the recognition of specific tumor peptides by cytotoxic T lymphocytes favoring cancer immune escape during natural tumor evolution. These alterations can be caused by genomic defects, such as loss of heterozygosity at chromosomes 6 and 15 (LOH-6 and LOH-15), where HLA class I genes are located. There is growing evidence indicating that LOH in HLA contributes to the immune selection of HLA loss variants and influences the resistance to immunotherapy. Nevertheless, the incidence and the mechanism of this chromosomal aberration involving HLA genes has not been systematically assessed in different types of tumors and often remains underestimated. Here, we used SNP arrays to investigate the incidence and patterns of LOH-6 and LOH-15 in a number of human cancer cell lines and tissues of different histological types. We observed that LOH in HLA is a common event in cancer samples with a prevalence of a copy neutral type of LOH (CN-LOH) that affects entire chromosome 6 or 15 and involves chromosomal duplications. LOH-6 was observed more often and was associated with homozygous HLA genotype and partial HLA loss of expression. We also discuss the immunologic and clinical implications of LOH in HLA on tumor clonal expansion and association with the cancer recurrence after treatment. Full article
(This article belongs to the Special Issue Genomic Instability in Tumor Evolution and Therapy Response)
Show Figures

Figure 1

Review

Jump to: Research

Review
Chemotherapy Side-Effects: Not All DNA Damage Is Equal
Cancers 2022, 14(3), 627; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14030627 (registering DOI) - 26 Jan 2022
Viewed by 132
Abstract
Recent advances have increased survival rates of children and adults suffering from cancer thanks to effective anti-cancer therapy, such as chemotherapy. However, during treatment and later in life they are frequently confronted with the severe negative side-effects of their life-saving treatment. The occurrence [...] Read more.
Recent advances have increased survival rates of children and adults suffering from cancer thanks to effective anti-cancer therapy, such as chemotherapy. However, during treatment and later in life they are frequently confronted with the severe negative side-effects of their life-saving treatment. The occurrence of numerous features of accelerated aging, seriously affecting quality of life, has now become one of the most pressing problems associated with (pediatric) cancer treatment. Chemotherapies frequently target and damage the DNA, causing mutations or genome instability, a major hallmark of both cancer and aging. However, there are numerous types of chemotherapeutic drugs that are genotoxic and interfere with DNA metabolism in different ways, each with their own biodistribution, kinetics, and biological fate. Depending on the type of DNA lesion produced (e.g., interference with DNA replication or RNA transcription), the organ or cell type inflicted (e.g., cell cycle or differentiation status, metabolic state, activity of clearance and detoxification mechanisms, the cellular condition or micro-environment), and the degree of exposure, outcomes of cancer treatment can largely differ. These considerations provide a conceptual framework in which different classes of chemotherapeutics contribute to the development of toxicities and accelerated aging of different organ systems. Here, we summarize frequently observed side-effects in (pediatric) ex-cancer patients and discuss which types of DNA damage might be responsible. Full article
(This article belongs to the Special Issue Genomic Instability in Tumor Evolution and Therapy Response)
Back to TopTop