Incorporating DNA Damage Response (DDR) Mechanisms in Cancer Systems: 2nd Edition

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

Deadline for manuscript submissions: 15 March 2025 | Viewed by 1222

Special Issue Editor


E-Mail Website
Guest Editor

Special Issue Information

Dear Colleagues,

This Special Issue is a continuation of our previous Special Issue titled “Incorporating DNA Damage Response (DDR) Mechanisms in Cancer Systems” (https://www.mdpi.com/journal/cancers/special_issues/ddr).

The chronic exposure of cells and organisms to exogenous (environmental) or endogenous stress can lead to the deterioration of defense and homeostatic mechanisms such antioxidants, DNA damage response (DDR) and immune responses. This phenomenon is fueled by the increasing and persistent genomic instability, which is considered to be one of the major detrimental effects of the different types of stresses originating from ionizing and non-ionizing radiations, replication problems, etc. From simple cellular systems to complex biological systems such tissues or organs, it is important to understand how each system responds to DNA damage, especially of a complex type, and the final short- and long-terms effects.

Authors are invited to submit manuscripts outlining the mechanisms or phenomena that can lead to any type of DDR induction in any biological system, or even method papers for the proper measurement of DDR and its biological outcomes. We live in the era of omics and big data; therefore, teams working in this field by means of bioinformatics, systems biology and machine learning, as well as any type of omics, are highly welcome.

In this Special Issue, we are reaching out for teams or groups working in many interdisciplinary fields toward a better understanding of the complexity of cancer evolution, especially regarding the role of malfunctioning DDR and its repair. Moreover, we expect contributions from groups working on the clinical aspects of DDR and its role in the regulation of homeostasis in the organism.

Prof. Dr. Alexandros Georgakilas
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 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 2900 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

  • complex DNA damage
  • methodologies for detection of DNA damage
  • DNA damage response (DDR) and repair
  • biological effects of radiation stress, oxidative stress, and replication stress
  • DDR and immune response
  • genomic instability
  • aging
  • bioinformatics and systems biology
  • machine learning and artificial intelligence
  • cancer survival and therapeutics
  • 3D bioprinting of cells and tissues

Benefits of Publishing in a Special Issue

  • Ease of navigation: Grouping papers by topic helps scholars navigate broad scope journals more efficiently.
  • Greater discoverability: Special Issues support the reach and impact of scientific research. Articles in Special Issues are more discoverable and cited more frequently.
  • Expansion of research network: Special Issues facilitate connections among authors, fostering scientific collaborations.
  • External promotion: Articles in Special Issues are often promoted through the journal's social media, increasing their visibility.
  • e-Book format: Special Issues with more than 10 articles can be published as dedicated e-books, ensuring wide and rapid dissemination.

Further information on MDPI's Special Issue polices can be found here.

Published Papers (1 paper)

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

Research

16 pages, 2818 KiB  
Article
Impact of Optimized Ku–DNA Binding Inhibitors on the Cellular and In Vivo DNA Damage Response
by Pamela L. Mendoza-Munoz, Narva Deshwar Kushwaha, Dineshsinha Chauhan, Karim Ben Ali Gacem, Joy E. Garrett, Joseph R. Dynlacht, Jean-Baptiste Charbonnier, Navnath S. Gavande and John J. Turchi
Cancers 2024, 16(19), 3286; https://doi.org/10.3390/cancers16193286 - 26 Sep 2024
Viewed by 1012
Abstract
Background: DNA-dependent protein kinase (DNA-PK) is a validated cancer therapeutic target involved in DNA damage response (DDR) and non-homologous end-joining (NHEJ) repair of DNA double-strand breaks (DSBs). Ku serves as a sensor of DSBs by binding to DNA ends and activating DNA-PK. [...] Read more.
Background: DNA-dependent protein kinase (DNA-PK) is a validated cancer therapeutic target involved in DNA damage response (DDR) and non-homologous end-joining (NHEJ) repair of DNA double-strand breaks (DSBs). Ku serves as a sensor of DSBs by binding to DNA ends and activating DNA-PK. Inhibition of DNA-PK is a common strategy to block DSB repair and improve efficacy of ionizing radiation (IR) therapy and radiomimetic drug therapies. We have previously developed Ku–DNA binding inhibitors (Ku-DBis) that block in vitro and cellular NHEJ activity, abrogate DNA-PK autophosphorylation, and potentiate cellular sensitivity to IR. Results and Conclusions: Here we report the discovery of oxindole Ku-DBis with improved cellular uptake and retained potent Ku-inhibitory activity. Variable monotherapy activity was observed in a panel of non-small cell lung cancer (NSCLC) cell lines, with ATM-null cells being the most sensitive and showing synergy with IR. BRCA1-deficient cells were resistant to single-agent treatment and antagonistic when combined with DSB-generating therapies. In vivo studies in an NSCLC xenograft model demonstrated that the Ku-DBi treatment blocked IR-dependent DNA-PKcs autophosphorylation, modulated DDR, and reduced tumor cell proliferation. This represents the first in vivo demonstration of a Ku-targeted DNA-binding inhibitor impacting IR response and highlights the potential therapeutic utility of Ku-DBis for cancer treatment. Full article
Show Figures

Figure 1

Back to TopTop