Open AccessA combination therapy for KRAS ‐mutant lung cancer by targeting synthetic lethal partners of mutant KRAS
Author(s) -
Pang Xiufeng,
Liu Mingyao
Publication year - 2016
Publication title -
cancer communications
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.119
H-Index - 53
ISSN - 2523-3548
DOI - 10.1186/s40880-016-0154-7
Subject(s) - kras , rhoa , mutant , cancer research , lung cancer , cancer , targeted therapy , kinase , plk1 , suppressor , cancer cell , biology , medicine , signal transduction , oncology , colorectal cancer , gene , genetics , cell cycle
The KRAS 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 undefined biological properties. As reported in the paper entitled “Suppression of KRas‐mutant cancer through the combined inhibition of KRAS with PLK1 and ROCK” in Nature Communications , 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 P21 WAF1/CIP1 contributed to the synergistic mechanism of the combination therapy. These findings open a novel avenue for the treatment of KRAS ‐mutant lung cancer.