Targeting DNA repair in cancer: current state and novel approaches

DNA damage response, DNA repair and genomic instability have been under study for their role in tumor initiation and progression for many years now. More recently, next-generation sequencing on cancer tissue from various patient cohorts have revealed mutations and epigenetic silencing of various gen...

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Bibliographic Details
Published in:Cellular and molecular life sciences : CMLS 2020-02, Vol.77 (4), p.677-703
Main Authors: Klinakis, Apostolos, Karagiannis, Dimitris, Rampias, Theodoros
Format: Article
Language:English
Subjects:
Animals
Antineoplastic Agents - pharmacology
Biochemistry
Biomedical and Life Sciences
Biomedicine
Cancer
Cell Biology
Clinical trials
Damage
Deoxyribonucleic acid
DNA
DNA damage
DNA Damage - drug effects
DNA repair
DNA Repair - drug effects
Drug Discovery - methods
Drugs
Epigenesis, Genetic - drug effects
Epigenetics
Gene Expression Regulation, Neoplastic - drug effects
Gene silencing
Genomic instability
Genomic Instability - drug effects
Humans
Immunotherapy
Immunotherapy - methods
Life Sciences
Mutation
Neoplasms - drug therapy
Neoplasms - genetics
Neoplasms - therapy
Next-generation sequencing
Poly(ADP-ribose) polymerase
Poly(ADP-ribose) Polymerase Inhibitors - pharmacology
Repair
Review
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Summary:DNA damage response, DNA repair and genomic instability have been under study for their role in tumor initiation and progression for many years now. More recently, next-generation sequencing on cancer tissue from various patient cohorts have revealed mutations and epigenetic silencing of various genes encoding proteins with roles in these processes. These findings, together with the unequivocal role of DNA repair in therapeutic response, have fueled efforts toward the clinical exploitation of research findings. The successful example of PARP1/2 inhibitors has also supported these efforts and led to numerous preclinical and clinical trials with a large number of small molecules targeting various components involved in DNA repair singularly or in combination with other therapies. In this review, we focus on recent considerations related to DNA damage response and new DNA repair inhibition agents. We then discuss how immunotherapy can collaborate with these new drugs and how epigenetic drugs can rewire the activity of repair pathways and sensitize cancer cells to DNA repair inhibition therapies.
ISSN:1420-682X
1420-9071
DOI:10.1007/s00018-019-03299-8