Topical Collection "Incorporating DNA Damage Response (DDR) Mechanisms in Cancer Systems"

Editor

Prof. Dr. Alexandros G. Georgakilas
E-Mail Website
Collection Editor
DNA Damage Laboratory, Physics Department, School of Applied Mathematical and Physical Sciences, National Technical University of Athens, Zografou Campus, 15780 Athens, Greece
Interests: radiation biology; cancer biology; DNA damage and repair; oxidative stress; Carcinogenesis; bioinformatics; systems biology
Special Issues and Collections in MDPI journals

Topical Collection Information

Dear Colleagues,

The chronic exposure of cells and organisms to exogenous (environmental) or endogenous stress can lead to the deterioration of the defense and homeostatic mechanisms, like antioxidants, DNA damage response (DDR), and immune response, which are strongly associated. This phenomenon is always 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, and others. From simple cellular systems to complex biological systems like tissues or organs, it is important to know how each system responds to DNA damage, especially of a complex type, and what are the final short- and long-terms effects?

Authors are invited to submit manuscripts dealing with 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 outcome. 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 Topical Collection, we are reaching out for teams or groups working in many interdisciplinary fields towards a better understanding of the complexity of cancer evolution, especially the role of malfunctioning DDR and its repair. We also 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
Collection 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 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 collection 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 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 1800 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

Published Papers (2 papers)

2019

Open AccessArticle
Antitumor Reactive T-Cell Responses Are Enhanced In Vivo by DAMP Prothymosin Alpha and Its C-Terminal Decapeptide
Cancers 2019, 11(11), 1764; https://doi.org/10.3390/cancers11111764 (registering DOI) - 09 Nov 2019
Abstract
Prothymosin α (proTα) and its C-terminal decapeptide proTα(100–109) were shown to pleiotropically enhance innate and adaptive immune responses. Their activities have been broadly studied in vitro, focusing primarily on the restoration of the deficient immunoreactivity of cancer patients’ leukocytes. Previously, we showed that [...] Read more.
Prothymosin α (proTα) and its C-terminal decapeptide proTα(100–109) were shown to pleiotropically enhance innate and adaptive immune responses. Their activities have been broadly studied in vitro, focusing primarily on the restoration of the deficient immunoreactivity of cancer patients’ leukocytes. Previously, we showed that proTα and proTα(100–109) act as danger-associated molecular patterns (DAMPs), ligate Toll-like receptor-4, signal through TRIF- and MyD88-dependent pathways, promote the maturation of dendritic cells and elicit T-helper type 1 (Th1) immune responses in vitro, leading to the optimal priming of tumor antigen-reactive T-cell functions. Herein, we assessed their activity in a preclinical melanoma model. Immunocompetent mice bearing B16.F1 tumors were treated with two cycles of proTα or proTα(100–109) together with a B16.F1-derived peptide vaccine. Coadministration of proTα or proTα(100–109) and the peptide vaccine suppressed melanoma-cell proliferation, as evidenced by reduced tumor-growth rates. Higher melanoma infiltration by CD3+ T cells was observed, whereas ex vivo analysis of mouse total spleen cells verified the in vivo induction of melanoma-reactive cytotoxic responses. Additionally, increased levels of proinflammatory and Th1-type cytokines were detected in mouse serum. We propose that, in the presence of tumor antigens, DAMPs proTα and proTα(100–109) induce Th1-biased immune responses in vivo. Their adjuvant ability to orchestrate antitumor immunoreactivities can eventually be exploited therapeutically in humans. Full article
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Figure 1

Open AccessArticle
Antileukemic Efficacy in Vitro of Talazoparib and APE1 Inhibitor III Combined with Decitabine in Myeloid Malignancies
Cancers 2019, 11(10), 1493; https://doi.org/10.3390/cancers11101493 - 03 Oct 2019
Abstract
Malignant hematopoietic cells of myelodysplastic syndromes (MDS)/chronic myelomonocytic leukemias (CMML) and acute myeloid leukemias (AML) may be vulnerable to inhibition of poly(ADP ribose) polymerase 1/2 (PARP1/2) and apurinic/apyrimidinic endonuclease 1 (APE1). PARP1/2 and APE1 are critical enzymes involved in single-strand break repair and [...] Read more.
Malignant hematopoietic cells of myelodysplastic syndromes (MDS)/chronic myelomonocytic leukemias (CMML) and acute myeloid leukemias (AML) may be vulnerable to inhibition of poly(ADP ribose) polymerase 1/2 (PARP1/2) and apurinic/apyrimidinic endonuclease 1 (APE1). PARP1/2 and APE1 are critical enzymes involved in single-strand break repair and base excision repair, respectively. Here, we investigated the cytotoxic efficacy of talazoparib and APE1 inhibitor III, inhibitors of PARP1/2 and APE1, in primary CD34+ MDS/CMML cell samples (n = 8; 4 MDS and 4 CMML) and in primary CD34+ or CD34− AML cell samples (n = 18) in comparison to healthy CD34+ donor cell samples (n = 8). Strikingly, talazoparib and APE1 inhibitor III demonstrated critical antileukemic efficacy in selected MDS/CMML and AML cell samples. Low doses of talazoparib and APE1 inhibitor III further increased the cytotoxic efficacy of decitabine in MDS/CMML and AML cells. Moreover, low doses of APE1 inhibitor III increased the cytotoxic efficacy of talazoparib in MDS/CMML and AML cells. In summary, talazoparib and APE1 inhibitor III demonstrated substantial antileukemic efficacy as single agents, in combination with decitabine, and combined with each other. Hence, our findings support further investigation of these agents in sophisticated clinical trials. Full article
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Figure 1

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