A combination therapy forKRAS-mutant lung cancer bytargeting synthetic lethal partners ofmutantKRAS
10.1186/s40880-016-0154-7
- Author:
Pang XIUFENG
1
;
Liu MINGYAO
Author Information
1. Shanghai Key Laboratory of Regulatory Biology
- Keywords:
Synthetic lethality;
KRAS;
Polo-like kinase 1;
RhoA/Rho kinase;
Combination therapy
- From:Chinese Journal of Cancer
2016;56(11):571-573
- CountryChina
- Language:Chinese
-
Abstract:
TheKRAS gene is frequently mutated in multiple cancer types, but it fell off the drug discovery radar for many years because of its inherent “undruggable” structure and undeifned biological properties. As reported in the paper entitled “Suppression of KRas-mutant cancer through the combined inhibition of KRAS with PLK1 and ROCK” inNature Com-munications, we performed a synthetic lethal screening with a combinatorial strategy on a panel of clinical drugs; we found that combined inhibition of polo-like kinase 1 and RhoA/Rho kinase markedly suppressed tumor growth in mice. An increase in the expression of the tumor suppressor P21WAF1/CIP1 contributed to the synergistic mechanism of the combination therapy. These ifndings open a novel avenue for the treatment ofKRAS-mutant lung cancer.
