About this Research Topic

Background

Although therapies that disrupt the DNA integrity of tumor cells have witnessed the advent of anti-cancer treatment, they continue to play a major role in cancer patient management as well as in the current era of personalized medicine. Combination approaches and specific molecular targeting are complementing classical radio- and chemotherapeutic regimens and novel radiation technologies, as well as ground-breaking discoveries regarding molecular drivers and specific cancer subtypes, continuously contribute to improved treatment outcomes.

Aberrant remodeling of the DNA damage response (DDR) machinery that results in loss of function of key signaling components, is an event that at first instance chronically contributes to cancer onset, progression, and therapeutic resistance. On the other hand, particular deficiencies in DNA damage signaling and DNA repair pathways have been recognized as a plausible Achilles heel of cancer and can be therapeutically exploited. Two of the most prominent examples that target pathways complementary to a genetic disadvantage include the use of PARP inhibitors to treat BRCA-negative cancers and the potential future application of CHK1 inhibition in the context of p53 loss-of-function-mutated tumors. Complex genomic characterizations of tumors and pipelines to test a variety of therapeutic options in laboratory conditions have the potential to enable identification of similar DDR vulnerabilities or treatment protocols that efficiently interfere with proper DDR on a single-patient scale before the actual start of the treatment.

We welcome original studies and review articles focusing on new aspects of modulation of DDR, synthetic lethality concepts and DNA repair pathways deficiencies in various types of cancer. Areas of interest include but are not limited to cell cycle modulators and cell fate decisions upon DNA damage, DNA damage-related mutational signatures and tumor characteristics, checkpoint kinase inhibitors and the installment of immunotherapy and molecular targeting in combination with DDR-based interventions. Novel insights into the effects of radiation therapy (photons, protons and co., treatment schedules modulations, radiosensitizers/radioprotectants), DDR and metabolism as well as omics approaches to study cellular DDR can also be covered. Besides studies focusing on roles of specific posttranslational modifications of known DDR proteins and master DDR kinases, discoveries and characterizations of new players in cellular DDR are of prime interest as well.

Topic Editor Christian Reinhardt has received funding from companies Gilead, and lecture fees from Abbvie, Merck, and AstraZeneca. All other topic editors declare no competing interests with regards to the Research Topic subject.

Keywords: DNA damage response, synthetic lethality, personalized medicine, DNA repair pathways, precision radiation oncology

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