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@article{1339332,
author = {Samadder, Pounami and Aithal, Rakesh and Beláň, Ondrej and Krejčí, Lumír},
article_location = {Kidlington},
article_number = {"May"},
doi = {http://dx.doi.org/10.1016/j.pharmthera.2016.02.007},
keywords = {DSB repair; genome instability; cancer; kinases; helicases; nucleases},
language = {eng},
issn = {0163-7258},
journal = {Pharmacology & Therapeutics},
title = {Cancer TARGETases: DSB Repair as a Pharmacological Target},
url = {http://www.sciencedirect.com/science/article/pii/S016372581600036X},
volume = {161},
year = {2016}
}
TY - JOUR
ID - 1339332
AU - Samadder, Pounami - Aithal, Rakesh - Beláň, Ondrej - Krejčí, Lumír
PY - 2016
TI - Cancer TARGETases: DSB Repair as a Pharmacological Target
JF - Pharmacology & Therapeutics
VL - 161
IS - "May"
SP - 111-131
EP - 111-131
PB - Pergamon-Elsevier Science LTD
SN - 01637258
KW - DSB repair
KW - genome instability
KW - cancer
KW - kinases
KW - helicases
KW - nucleases
UR - http://www.sciencedirect.com/science/article/pii/S016372581600036X
N2 - 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 are 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 present 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.
ER -
SAMADDER, Pounami, Rakesh AITHAL, Ondrej BELÁŇ and Lumír KREJČÍ. Cancer TARGETases: DSB Repair as a Pharmacological Target. \textit{Pharmacology \&{} Therapeutics}. Kidlington: Pergamon-Elsevier Science LTD, 2016, vol.~161, ''May'', p.~111-131. ISSN~0163-7258. Available from: https://dx.doi.org/10.1016/j.pharmthera.2016.02.007.
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