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Biomedicines
Special Issues
Evolving Landscape of DNA Repair in Cancer Therapy
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Evolving Landscape of DNA Repair in Cancer Therapy

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Cancer Biology and Oncology".

Deadline for manuscript submissions: closed (31 December 2023) | Viewed by 17347

Special Issue Editor

Dr. Yi Chieh Lim

E-Mail Website
Guest Editor
Brain Tumor Biology, Danish Cancer Research Center (DCRC), 2100 Copenhagen, Denmark
Interests: pharmacotherapeutics; genome instability; DNA repair; neuro-oncology; system biology; biomarkers
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Cancer is fundamentally a disease of the genome that is reliant on a compromised DNA damage response (DDR) network to promote oncogenic transformation. Despite the need to undergo mutagenic changes, tumor cells are dependent on a repertoire of DNA repair mechanisms to maintain genome integrity and mediate resistance against genotoxic drugs. With the availability of high-throughput omics data, precision medicine can gain better insights into individual tumor profiles. By detecting vulnerabilities in the different DNA repair pathways, specific targeting can be implemented to eradicate tumor growth.

For this Special Issue, we are interested in featuring original research and review articles that focus on mammalian genome instability pathways and/or the links between DNA repair and cancer.

The articles that are suitable for this topic include:

  • Identifying novel DNA repair factors involved in the sensing, signaling, and restoration of DNA damage.
  • Developing single or combinational therapeutics that target DNA damage signaling and/or repair pathways.
  • Advances in DNA damage response and/repair biomarkers for precision medicine.
  • Intrinsic and acquired resistant profiles of DNA damage response in cancer.
  • Methodology in defining new approaches to measure DNA repair and DNA damage.

Dr. Yi Chieh Lim
Guest Editor

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. Biomedicines is an international peer-reviewed open access monthly 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 2600 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

  • DNA damage response
  • DNA repair
  • genomic instability
  • cancer
  • chemotherapeutics
  • biomarkers
  • synthetic lethality
  • precision medicine
  • therapeutic resistance
  • theranostics

Published Papers (6 papers)

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Research

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16 pages, 2339 KiB  
Article
Mitomycin C in Homologous Recombination Deficient Metastatic Pancreatic Cancer after Disease Progression on Platinum-Based Chemotherapy and Olaparib
by Gehan Botrus, Denise Roe, Gayle S. Jameson, Pedro Luiz Serrano Uson Junior, Ronald Lee Korn, Lana Caldwell, Taylor Bargenquast, Max Miller and Erkut Hasan Borazanci
Biomedicines 2022, 10(11), 2705; https://doi.org/10.3390/biomedicines10112705 - 26 Oct 2022
Cited by 1 | Viewed by 1695
Abstract
Recent efforts to personalize treatment with platinum-based chemotherapy and PARP inhibitors have produced promising results in homologous recombinant deficient (HRD) metastatic pancreatic cancer (MPC). However, new strategies are necessary to overcome resistance. The below case series documents patients treated at the HonorHealth Research [...] Read more.
Recent efforts to personalize treatment with platinum-based chemotherapy and PARP inhibitors have produced promising results in homologous recombinant deficient (HRD) metastatic pancreatic cancer (MPC). However, new strategies are necessary to overcome resistance. The below case series documents patients treated at the HonorHealth Research Institute with a diagnosis of HRD MPC who received Mitomycin C (MMC) treatment from January 2013 until July 2018. Five HRD MPC patients treated with MMC were evaluated. All patients received at least one course of treatment. Mean age at MMC treatment initiation was 58 years. There were 3 females and 2 males. All patients had tumors that progressed on platinum-based chemotherapy, four patients had previous exposure to Olaparib. The median PFS was 10.1 months, and the median OS was 12.3 months. Responses were observed only in patients harboring BRCA2 mutations, no response was observed in the PALB2 mutation carrier. MMC in this heavily previously treated PC was safe, with overall manageable grade 2 gastrointestinal toxicities including nausea and vomiting, and G3 hematological toxicities including anemia and thrombocytopenia. Pancreatic cancer patients with HRD may benefit from MMC treatment. Further clinical investigation of MMC in pancreatic cancer is warranted. Full article
(This article belongs to the Special Issue Evolving Landscape of DNA Repair in Cancer Therapy)
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14 pages, 2968 KiB  
Article
Dynamic Interplay between Cockayne Syndrome Protein B and Poly(ADP-Ribose) Polymerase 1 during Oxidative DNA Damage Repair
by Robert J. Lake, Rabeya Bilkis and Hua-Ying Fan
Biomedicines 2022, 10(2), 361; https://doi.org/10.3390/biomedicines10020361 - 2 Feb 2022
Cited by 4 | Viewed by 1622
Abstract
Oxidative stress contributes to numerous diseases, including cancer. CSB is an ATP-dependent chromatin remodeler critical for oxidative stress relief. PARP1 is the major sensor for DNA breaks and fundamental for efficient single-strand break repair. DNA breaks activate PARP1, leading to the synthesis of [...] Read more.
Oxidative stress contributes to numerous diseases, including cancer. CSB is an ATP-dependent chromatin remodeler critical for oxidative stress relief. PARP1 is the major sensor for DNA breaks and fundamental for efficient single-strand break repair. DNA breaks activate PARP1, leading to the synthesis of poly(ADP-ribose) (PAR) on itself and neighboring proteins, which is crucial for the recruitment of DNA repair machinery. CSB and PARP1 interact; however, how CSB mechanistically participates in oxidative DNA damage repair mediated by PARP1 remains unclear. Using chromatin immunoprecipitation followed by quantitative PCR, we found that CSB and PARP1 facilitate each other’s chromatin association during the onset of oxidative stress, and that CSB facilitates PARP1 removal when the level of chromatin-bound CSB increases. Furthermore, by monitoring chromatin PAR levels using Western blot analysis, we found that CSB sustains the DNA damage signal initiated by PARP1, and may prevent PARP1 overactivation by facilitating DNA repair. By assaying cell viability in response to oxidative stress, we further demonstrate that PARP1 regulation by CSB is a major CSB function in oxidatively-stressed cells. Together, our study uncovers a dynamic interplay between CSB and PARP1 that is critical for oxidative stress relief. Full article
(This article belongs to the Special Issue Evolving Landscape of DNA Repair in Cancer Therapy)
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16 pages, 3344 KiB  
Article
DNArepairK: An Interactive Database for Exploring the Impact of Anticancer Drugs onto the Dynamics of DNA Repair Proteins
by Yordan Babukov, Radoslav Aleksandrov, Aneliya Ivanova, Aleksandar Atemin and Stoyno Stoynov
Biomedicines 2021, 9(9), 1238; https://doi.org/10.3390/biomedicines9091238 - 16 Sep 2021
Cited by 6 | Viewed by 1991
Abstract
Cells are constantly exposed to numerous mutagens that produce diverse types of DNA lesions. Eukaryotic cells have evolved an impressive array of DNA repair mechanisms that are able to detect and repair these lesions, thus preventing genomic instability. The DNA repair process is [...] Read more.
Cells are constantly exposed to numerous mutagens that produce diverse types of DNA lesions. Eukaryotic cells have evolved an impressive array of DNA repair mechanisms that are able to detect and repair these lesions, thus preventing genomic instability. The DNA repair process is subjected to precise spatiotemporal coordination, and repair proteins are recruited to lesions in an orderly fashion, depending on their function. Here, we present DNArepairK, a unique open-access database that contains the kinetics of recruitment and removal of 70 fluorescently tagged DNA repair proteins to complex DNA damage sites in living HeLa Kyoto cells. An interactive graphical representation of the data complemented with live cell imaging movies facilitates straightforward comparisons between the dynamics of proteins contributing to different DNA repair pathways. Notably, most of the proteins included in DNArepairK are represented by their kinetics in both nontreated and PARP1/2 inhibitor-treated (talazoparib) cells, thereby providing an unprecedented overview of the effects of anticancer drugs on the regular dynamics of the DNA damage response. We believe that the exclusive dataset available in DNArepairK will be of value to scientists exploring the DNA damage response but, also, to inform and guide the development and evaluation of novel DNA repair-targeting anticancer drugs. Full article
(This article belongs to the Special Issue Evolving Landscape of DNA Repair in Cancer Therapy)
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Review

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19 pages, 1440 KiB  
Review
Role of Base Excision Repair in Innate Immune Cells and Its Relevance for Cancer Therapy
by Shengyuan Zhao, Samy L. Habib, Alireza G. Senejani, Manu Sebastian and Dawit Kidane
Biomedicines 2022, 10(3), 557; https://doi.org/10.3390/biomedicines10030557 - 26 Feb 2022
Cited by 3 | Viewed by 2809
Abstract
Innate immunity is critical for immediate recognition and elimination of invading pathogens or defense against cancer cell growth. Dysregulation of innate immune systems is associated with the pathogenesis of different types of inflammatory diseases, including cancer. In addition, the maintenance of innate immune [...] Read more.
Innate immunity is critical for immediate recognition and elimination of invading pathogens or defense against cancer cell growth. Dysregulation of innate immune systems is associated with the pathogenesis of different types of inflammatory diseases, including cancer. In addition, the maintenance of innate immune cells’ genomic integrity is crucial for the survival of all organisms. Oxidative stress generated from innate immune cells may cause self-inflicted DNA base lesions as well as DNA damage on others neighboring cells, including cancer cells. Oxidative DNA base damage is predominantly repaired by base excision repair (BER). BER process different types of DNA base lesions that are presented in cancer and innate immune cells to maintain genomic integrity. However, mutations in BER genes lead to impaired DNA repair function and cause insufficient genomic integrity. Moreover, several studies have implicated that accumulation of DNA damage leads to chromosomal instability that likely activates the innate immune signaling. Furthermore, dysregulation of BER factors in cancer cells modulate the infiltration of innate immune cells to the tumor microenvironment. In the current review, the role of BER in cancer and innate immune cells and its impact on innate immune signaling within the tumor microenvironment is summarized. This is a special issue that focuses on DNA damage and cancer therapy to demonstrate how BER inhibitor or aberrant repair modulates innate inflammatory response and impact immunotherapy approaches. Overall, the review provides substantial evidence to understand the impact of BER in innate immune response dynamics within the current immune-based therapeutic strategy. Full article
(This article belongs to the Special Issue Evolving Landscape of DNA Repair in Cancer Therapy)
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16 pages, 1169 KiB  
Review
Therapeutic Opportunities of Disrupting Genome Integrity in Adult Diffuse Glioma
by Diana Aguilar-Morante, Daniel Gómez-Cabello, Hazel Quek, Tianqing Liu, Petra Hamerlik and Yi Chieh Lim
Biomedicines 2022, 10(2), 332; https://doi.org/10.3390/biomedicines10020332 - 31 Jan 2022
Cited by 1 | Viewed by 3092
Abstract
Adult diffuse glioma, particularly glioblastoma (GBM), is a devastating tumor of the central nervous system. The existential threat of this disease requires on-going treatment to counteract tumor progression. The present outcome is discouraging as most patients will succumb to this disease. The low [...] Read more.
Adult diffuse glioma, particularly glioblastoma (GBM), is a devastating tumor of the central nervous system. The existential threat of this disease requires on-going treatment to counteract tumor progression. The present outcome is discouraging as most patients will succumb to this disease. The low cure rate is consistent with the failure of first-line therapy, radiation and temozolomide (TMZ). Even with their therapeutic mechanism of action to incur lethal DNA lesions, tumor growth remains undeterred. Delivering additional treatments only delays the inescapable development of therapeutic tolerance and disease recurrence. The urgency of establishing lifelong tumor control needs to be re-examined with a greater focus on eliminating resistance. Early genomic and transcriptome studies suggest each tumor subtype possesses a unique molecular network to safeguard genome integrity. Subsequent seminal work on post-therapy tumor progression sheds light on the involvement of DNA repair as the causative contributor for hypermutation and therapeutic failure. In this review, we will provide an overview of known molecular factors that influence the engagement of different DNA repair pathways, including targetable vulnerabilities, which can be exploited for clinical benefit with the use of specific inhibitors. Full article
(This article belongs to the Special Issue Evolving Landscape of DNA Repair in Cancer Therapy)
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13 pages, 2412 KiB  
Review
UV Radiation in DNA Damage and Repair Involving DNA-Photolyases and Cryptochromes
by Yuliya L. Vechtomova, Taisiya A. Telegina, Andrey A. Buglak and Mikhail S. Kritsky
Biomedicines 2021, 9(11), 1564; https://doi.org/10.3390/biomedicines9111564 - 28 Oct 2021
Cited by 34 | Viewed by 5016
Abstract
Prolonged exposure to ultraviolet radiation on human skin can lead to mutations in DNA, photoaging, suppression of the immune system, and other damage up to skin cancer (melanoma, basal cell, and squamous cell carcinoma). We reviewed the state of knowledge of the damaging [...] Read more.
Prolonged exposure to ultraviolet radiation on human skin can lead to mutations in DNA, photoaging, suppression of the immune system, and other damage up to skin cancer (melanoma, basal cell, and squamous cell carcinoma). We reviewed the state of knowledge of the damaging action of UVB and UVA on DNA, and also the mechanisms of DNA repair with the participation of the DNA-photolyase enzyme or of the nucleotide excision repair (NER) system. In the course of evolution, most mammals lost the possibility of DNA photoreparation due to the disappearance of DNA photolyase genes, but they retained closely related cryptochromes that regulate the transcription of the NER system enzymes. We analyze the published relationships between DNA photolyases/cryptochromes and carcinogenesis, as well as their possible role in the prevention and treatment of diseases caused by UV radiation. Full article
(This article belongs to the Special Issue Evolving Landscape of DNA Repair in Cancer Therapy)
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