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DNA Damage Repair in Cancer: Genetics, Molecular Mechanisms, Diagnostic and Therapeutic Perspectives

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Oncology".

Deadline for manuscript submissions: 30 April 2024 | Viewed by 5471

Special Issue Editors

Dr. Dana Jurkovičová

E-Mail Website
Guest Editor
Cancer Research Institute, Biomedical Research Center, Slovak Academy of Sciences, Dubravska cesta 9, 845 05 Bratislava, Slovakia
Interests: cancer; genetics; epigenetics; DNA damage and repair; mitochondria; therapy resistance; intracellular signaling; biomarkers; targeted therapy
Dr. Ana Cristina Gonçalves

E-Mail Website
Guest Editor
Faculty of Medicine, Laboratory of Oncobiology and Hematology, Institute for Clinical and Biomedical Research (iCBR)—Area of Environment Genetics and Oncobiology (CIMAGO), University of Coimbra, 3000-548 Coimbra, Portugal
Interests: hematologic diseases; oncobiology; oncogenetics/epigenetics; nutrition; drug resistance; DNA damage repair; cancer metabolism; targeted therapies; translational research; personalized oncology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

DNA damage response (DDR) plays a crucial role in genome integrity preservation. Changes in DNA damage signaling pathways, DNA repair, and DNA recombination, among other mechanisms, can potentially lead to genomic instability, increase susceptibility to cancer, and influence cancer treatment. Genome instability is a well-established hallmark of cancer, also showing a role in tumor sensitivity and resistance to cancer therapy (including chemotherapy and radiation). Since genome instability, mutation burden, and DNA repair efficiency in cancer cells may have prognostic and predictive value, they also provide a portfolio of new molecular targets and treatment strategies in cancer. The clinical success of PARP inhibitors as a personalized treatment of cancers with defective homologous recombination repair highlights the role of DNA repair pathways.

We invite researchers to submit research and review articles addressing various issues DNA repair in cancer, including but not limited to the following topics:

  • DNA damage and repair as mechanisms of carcinogenesis
  • DDR in cancer biology
  • Role of DNA damage and repair in cancer diagnosis and prognosis
  • DNA repair as a molecular target and therapeutic option in cancer

Dr. Dana Jurkovičová
Dr. Ana Cristina Gonçalves
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 submissions that pass pre-check are 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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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

  • DNA damage and repair
  • genomic instability
  • cancer therapy
  • cancer resistance
  • biomarkers

Published Papers (3 papers)

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Research

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13 pages, 3121 KiB  
Article
HSPs/STAT3 Interplay Sustains DDR and Promotes Cytokine Release by Primary Effusion Lymphoma Cells
by Roberta Gonnella, Andrea Arena, Roberta Zarrella, Maria Saveria Gilardini Montani, Roberta Santarelli and Mara Cirone
Int. J. Mol. Sci. 2023, 24(4), 3933; https://doi.org/10.3390/ijms24043933 - 15 Feb 2023
Cited by 4 | Viewed by 1241
Abstract
Primary effusion lymphoma (PEL) is a rare and aggressive B-cell lymphoma, against which current therapies usually fail. In the present study, we show that targeting HSPs, such as HSP27, HSP70 and HSP90, could be an efficient strategy to reduce PEL cell survival, as [...] Read more.
Primary effusion lymphoma (PEL) is a rare and aggressive B-cell lymphoma, against which current therapies usually fail. In the present study, we show that targeting HSPs, such as HSP27, HSP70 and HSP90, could be an efficient strategy to reduce PEL cell survival, as it induces strong DNA damage, which correlated with an impairment of DDR. Moreover, as HSP27, HSP70 and HSP90 cross talk with STAT3, their inhibition results in STAT3 de-phosphorylation and. On the other hand, the inhibition of STAT3 may downregulate these HSPs. These findings suggest that targeting HSPs has important implications in cancer therapy, as it can reduce the release of cytokines by PEL cells, which, besides affecting their own survival, could negatively influence anti-cancer immune response. Full article
(This article belongs to the Special Issue DNA Damage Repair in Cancer: Genetics, Molecular Mechanisms, Diagnostic and Therapeutic Perspectives)
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Review

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13 pages, 486 KiB  
Review
Homologous Recombination Deficiency (HRD) in Cutaneous Oncology
by Favour A. Akinjiyan, Renee Morecroft, Jordan Phillipps, Tolulope Adeyelu, Andrew Elliott, Soo J. Park, Omar H. Butt, Alice Y. Zhou and George Ansstas
Int. J. Mol. Sci. 2023, 24(13), 10771; https://doi.org/10.3390/ijms241310771 - 28 Jun 2023
Viewed by 2063
Abstract
Skin cancers, including basal cell carcinoma (BCC), cutaneous squamous cell carcinoma (SCC), and melanoma, are the most common malignancies in the United States. Loss of DNA repair pathways in the skin plays a significant role in tumorigenesis. In recent years, targeting DNA repair [...] Read more.
Skin cancers, including basal cell carcinoma (BCC), cutaneous squamous cell carcinoma (SCC), and melanoma, are the most common malignancies in the United States. Loss of DNA repair pathways in the skin plays a significant role in tumorigenesis. In recent years, targeting DNA repair pathways, particularly homologous recombination deficiency (HRD), has emerged as a potential therapeutic approach in cutaneous malignancies. This review provides an overview of DNA damage and repair pathways, with a focus on HRD, and discusses major advances in targeting these pathways in skin cancers. Poly(ADP-ribose) polymerase (PARP) inhibitors have been developed to exploit HRD in cancer cells. PARP inhibitors disrupt DNA repair mechanisms by inhibiting PARP enzymatic activity, leading to the accumulation of DNA damage and cell death. The concept of synthetic lethality has been demonstrated in HR-deficient cells, such as those with BRCA1/2 mutations, which exhibit increased sensitivity to PARP inhibitors. HRD assessment methods, including genomic scars, RAD51 foci formation, functional assays, and BRCA1/2 mutation analysis, are discussed as tools for identifying patients who may benefit from PARP inhibitor therapy. Furthermore, HRD has been implicated in the response to immunotherapy, and the combination of PARP inhibitors with immunotherapy has shown promising results. The frequency of HRD in melanoma ranges from 18% to 57%, and studies investigating the use of PARP inhibitors as monotherapy in melanoma are limited. Further research is warranted to explore the potential of PARP inhibition in melanoma treatment. Full article
(This article belongs to the Special Issue DNA Damage Repair in Cancer: Genetics, Molecular Mechanisms, Diagnostic and Therapeutic Perspectives)
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22 pages, 1193 KiB  
Review
The Current Status of DNA-Repair-Directed Precision Oncology Strategies in Epithelial Ovarian Cancers
by Hiu Tang, Sanat Kulkarni, Christina Peters, Jasper Eddison, Maryam Al-Ani and Srinivasan Madhusudan
Int. J. Mol. Sci. 2023, 24(8), 7293; https://doi.org/10.3390/ijms24087293 - 14 Apr 2023
Cited by 3 | Viewed by 1580
Abstract
Survival outcomes for patients with advanced ovarian cancer remain poor despite advances in chemotherapy and surgery. Platinum-based systemic chemotherapy can result in a response rate of up to 80%, but most patients will have recurrence and die from the disease. Recently, the DNA-repair-directed [...] Read more.
Survival outcomes for patients with advanced ovarian cancer remain poor despite advances in chemotherapy and surgery. Platinum-based systemic chemotherapy can result in a response rate of up to 80%, but most patients will have recurrence and die from the disease. Recently, the DNA-repair-directed precision oncology strategy has generated hope for patients. The clinical use of poly(ADP-ribose) polymerase (PARP) inhibitors in BRCA germ-line-deficient and/or platinum-sensitive epithelial ovarian cancers has improved survival. However, the emergence of resistance is an ongoing clinical challenge. Here, we review the current clinical state of PARP inhibitors and other clinically viable targeted approaches in epithelial ovarian cancers. Full article
(This article belongs to the Special Issue DNA Damage Repair in Cancer: Genetics, Molecular Mechanisms, Diagnostic and Therapeutic Perspectives)
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