RAS-PI3K alpha interaction

The **RAS-PI3K alpha interaction** refers to the physical and functional association between members of the RAS family of small GTPases (notably KRAS, NRAS, HRAS, RRAS2, MRAS) and the catalytic subunit of phosphatidylinositol 3-kinase alpha (PI3Kα, encoded by PIK3CA, with the main catalytic subunit called p110α)[1][2][3][7]. This interaction specifically occurs at the RAS-binding domain (RBD) of p110α and is crucial for full activation of the PI3K-AKT-mTOR signaling pathway, which regulates cell growth, proliferation, angiogenesis, and survival[1][5]. Mutations in both RAS and PI3Kα are common oncogenic drivers, and their interaction is essential for RAS-driven tumorigenesis in certain cancers (e.g., lung, skin, colon, endometrial)[1][2]. Disrupting this protein-protein interaction has been shown in preclinical models to reduce tumor growth, enhance survival, and potentially overcome resistance to PI3K or MEK inhibitors. Research efforts, including drug discovery programs (e.g., BBO-10203), are ongoing to develop inhibitors that selectively inhibit this interaction for cancer therapy with a favorable safety profile[1][4][6].

Other names

RAS-PI3Kα interactionRAS-p110 alpha interactionRAS-PIK3CA interaction

Small molecule disrupts the physical interaction between RAS (such as KRAS) and PI3Kα (p110α catalytic subunit), inhibiting downstream oncogenic signaling (PI3K-AKT-mTOR pathway)[1][4][6] - Inhibitors targeting PI3Kα itself also indirectly affect RAS-PI3Kα signaling