Mutationally activated PIK3CAH1047R cooperates with BRAF V600E to promote lung cancer progression

Abstract

Adenocarcinoma of the lung, a leading cause of cancer death, frequently displays mutational activation of the KRAS proto-oncogene but, unlike lung cancers expressing mutated EGFR, ROS1, or ALK, there is no pathway-targeted therapy for patients with KRAS-mutated lung cancer. In preclinical models, expression of oncogenic KRASG12D in the lung epithelium of adult mice initiates development of lung adenocarcinoma through activation of downstream signaling pathways. In contrast, mutationally activated BRAFV600E, a KRAS effector, fails to initiate lung carcinogenesis despite highly efficient induction of benign lung tumorigenesis. To test if phosphoinositide 3-kinase (PI3K)-α (PIK3CA), another KRA..