Cancer TARGETases: DSB Repair as a Pharmacological Target

J 2016

Cancer TARGETases: DSB Repair as a Pharmacological Target

SAMADDER, Pounami, Rakesh AITHAL, Ondrej BELÁŇ and Lumír KREJČÍ

Basic information

Original name

Cancer TARGETases: DSB Repair as a Pharmacological Target

Authors

SAMADDER, Pounami (356 India, belonging to the institution), Rakesh AITHAL (356 India, belonging to the institution), Ondrej BELÁŇ (703 Slovakia, belonging to the institution) and Lumír KREJČÍ (203 Czech Republic, belonging to the institution)

Edition

Pharmacology & Therapeutics, Kidlington, Pergamon-Elsevier Science LTD, 2016, 0163-7258

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10600 1.6 Biological sciences

Country of publisher

United Kingdom of Great Britain and Northern Ireland

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 11.127

RIV identification code

RIV/00216224:14110/16:00087848

Organization unit

Faculty of Medicine

DOI

http://dx.doi.org/10.1016/j.pharmthera.2016.02.007

UT WoS

000375886600009

Keywords in English

DSB repair; genome instability; cancer; kinases; helicases; nucleases

Abstract

V originále

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.

Links

GAP207/12/2323, research and development project

Name: Endonuleazová a translokázová aktivita v restričních-modifikáčních komplexéch typu I

Investor: Czech Science Foundation

GA13-26629S, research and development project

Name: SUMO a stability genomu

Investor: Czech Science Foundation

MUNI/M/1894/2014, interní kód MU

Name: Development of new MUS81 nuclease inhibitors as chemical biology probe with clinical progression

Investor: Masaryk University, INTERDISCIPLINARY - Interdisciplinary research projects

NV15-33999A, research and development project

Name: Vývoj nových nízkomolekulárních protinádorových léčiv na principu syntetické letality

Citovat

SAMADDER, Pounami, Rakesh AITHAL, Ondrej BELÁŇ and Lumír KREJČÍ. Cancer TARGETases: DSB Repair as a Pharmacological Target. 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.

@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.

Detailed Information on Publication Record