Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
5844097 | Pharmacology & Therapeutics | 2016 | 110 Pages |
Abstract
Cancer is a disease attributed to the accumulation of DNA damages due to incapacitation of DNA repair pathways resulting in genomic instability and a mutator phenotype. Among the DNA lesions, double stranded breaks (DSBs) are the most toxic forms of DNA damage which may arise as a result of extrinsic DNA damaging agents or intrinsic replication stress in fast proliferating cancer cells. Accurate repair of DSBs is therefore paramount to the cell survival, and several classes of proteins such as kinases, nucleases, helicases or core recombinational proteins have pre-defined jobs in precise execution of DSB repair pathways. On one hand, the proper functioning of these proteins ensures maintenance of genomic stability in normal cells, and on the other hand results in resistance to various drugs employed in cancer therapy and therefore presents a suitable opportunity for therapeutic targeting. Higher relapse and resistance in cancer patients due to non-specific, cytotoxic therapies is an alarming situation and it is becoming more evident to employ personalized treatment based on the genetic landscape of the cancer cells. For the success of personalized treatment, it is of immense importance to identify more suitable targetable proteins in DSB repair pathways and also to explore new synthetic lethal interactions with these pathways. Here we review the various alternative approaches to target the various protein classes termed as cancer TARGETases in DSB repair pathway to obtain more beneficial and selective therapy.
Keywords
CDKTNBC5-FUATRMMCDDRTLSSSAshRNAmTORSSLHSP90NHEJALTG-quadruplexBERBLMDSBsNBSMRNMMRICLMitomycin CCLLEXO1FOXM1RPAforkhead box protein M1RRM1HRDCDNA-PKPARP153BP1Topoisomerase IIDNA2XRCC1Phosphatidylinositol 3-KinasesDNA polymerase etaXRCC3MMEJExonuclease 1WRNMRE11PI3KsHelicasesDSS1CtIPFEN1PCNAAMLX-Ray Repair Cross-Complementing Protein 1Ataxia–TelangiectasiaRQCDNA interstrand crosslinkMre11–Rad50–Nbs1 complexPol ηBRCA1/2DNA double-strand breaksMitochondrial DNADNA polymerase betaNERNucleasesSmall interfering RNAshort hairpin RNAsiRNAAdenosine TriphosphateATPProliferating Cell Nuclear AntigenHolliday junctionSingle-strand annealingGenome instabilityionizing radiationDSB repairnucleotide excision repairmismatch repairbase excision repairreplication protein ATopo IIATMmtDNACancerTriple negative breast cancertranslesion synthesisNijmegen breakage syndromenon-homologous end joiningAtriFlap endonuclease 15-fluorouracilacute myeloid leukemiaChronic lymphocytic leukemiaHomologous recombinationmammalian target of rapamycinHydroxyureaDNA-dependent protein kinaseDNA damage responseHIVhuman immunodeficiency virusHeat-shock protein 90pol βmicrohomology-mediated end joiningFanconi anemiaPolo-like kinasesKinasescyclin-dependent kinase
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Authors
Pounami Samadder, Rakesh Aithal, Ondrej Belan, Lumir Krejci,