The PI3K signaling pathway regulates diverse cellular processes, including proliferation, survival, and metabolism, and is aberrantly activated in human cancer. As such, numerous compounds targeting the PI3K pathway are currently being clinically evaluated for the treatment of cancer, and several have shown some early indications of efficacy in breast cancer. However, resistance against these agents, both de novo and acquired, may ultimately limit the efficacy of these compounds. Here, we have taken a systematic functional approach to uncovering potential mechanisms of resistance to PI3K inhibitors and have identified several genes whose expression promotes survival under conditions of PI3K/mammalian target of rapamycin (PI3K/mTOR) blockade, including the ribosomal S6 kinases
Violeta Serra, Pieter J.A. Eichhorn, Celina García-García, Yasir H. Ibrahim, Ludmila Prudkin, Gertrudis Sánchez, Olga Rodríguez, Pilar Antón, Josep-Lluís Parra, Sara Marlow, Maurizio Scaltriti, José Pérez-Garcia, Aleix Prat, Joaquín Arribas, William C. Hahn, So Young Kim, José Baselga
Overview of ORF kinase screen.