Cancer TARGETases: DSB Repair as a Pharmacological Target

J 2016

Cancer TARGETases: DSB Repair as a Pharmacological Target

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

Základní údaje

Originální název

Cancer TARGETases: DSB Repair as a Pharmacological Target

Autoři

SAMADDER, Pounami (356 Indie, domácí), Rakesh AITHAL (356 Indie, domácí), Ondrej BELÁŇ (703 Slovensko, domácí) a Lumír KREJČÍ (203 Česká republika, domácí)

Vydání

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

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

10600 1.6 Biological sciences

Stát vydavatele

Velká Británie a Severní Irsko

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 11.127

Kód RIV

RIV/00216224:14110/16:00087848

Organizační jednotka

Lékařská fakulta

DOI

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

UT WoS

000375886600009

Klíčová slova anglicky

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

Štítky

EL OK, podil

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 5. 10. 2016 16:24, Ing. Mgr. Věra Pospíšilíková

Anotace

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.

Návaznosti

GAP207/12/2323, projekt VaV

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

Investor: Grantová agentura ČR, Endonuleázová a translokázová aktivita v restrikčních-modifikačních komplexech typu I

GA13-26629S, projekt VaV

Název: SUMO a stability genomu

Investor: Grantová agentura ČR, SUMO a stability genomu

MUNI/M/1894/2014, interní kód MU

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

Investor: Masarykova univerzita, Development of new MUS81 nuclease inhibitors as chemical biology probe with clinical progression, INTERDISCIPLINARY - Mezioborové výzkumné projekty

NV15-33999A, projekt VaV

Název: Vývoj nových nízkomolekulárních protinádorových léčiv na principu syntetické letality

Citovat

SAMADDER, Pounami, Rakesh AITHAL, Ondrej BELÁŇ a Lumír KREJČÍ. Cancer TARGETases: DSB Repair as a Pharmacological Target. Pharmacology & Therapeutics. Kidlington: Pergamon-Elsevier Science LTD, 2016, roč. 161, "May", s. 111-131. ISSN 0163-7258. Dostupné z: 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 a Lumír KREJČÍ. Cancer TARGETases: DSB Repair as a Pharmacological Target. \textit{Pharmacology \&{} Therapeutics}. Kidlington: Pergamon-Elsevier Science LTD, 2016, roč.~161, ''May'', s.~111-131. ISSN~0163-7258. Dostupné z: https://dx.doi.org/10.1016/j.pharmthera.2016.02.007.

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