Article
A Preexisting Rare PIK3CAE545K Subpopulation Confers Clinical Resistance to MEK plus CDK4/6 Inhibition in NRAS Melanoma and Is Dependent on S6K1 Signaling.
Cancer discovery - 1 May 2018
Romano Gabriele, Chen Pei-Ling, Song Ping, McQuade Jennifer L, Liang Roger J, Liu Mingguang, Roh Whijae, Duose Dzifa Y, Carapeto Fernando C L, Li Jun, Teh Jessica L F, Aplin Andrew E, Chen Merry, Zhang Jianhua, Lazar Alexander J, Davies Michael A, Futreal P Andrew, Amaria Rodabe N, Zhang David Y, Wargo Jennifer A, Kwong Lawrence N
Abstract excerpt
Combined MEK and CDK4/6 inhibition (MEKi + CDK4i) has shown promising clinical outcomes in patients with NRAS-mutant melanoma. Here, we interrogated longitudinal biopsies from a patient who initially responded to MEKi + CDK4i therapy but subsequently developed resistance. Whole-exome sequencing and functional validation identified an acquired PIK3CAE545K mutation as conferring drug resistance. We demonstrate that...
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