title: Targeting therapeutic liabilities engendered by PIK3R1 mutations for cancer treatment.
abstract: The regulatory subunit of PI3K, p85α (encoded by PIK3R1), binds, stabilizes and inhibits the PI3K p110 catalytic subunit. Functional characterization of PIK3R1 mutations has identified not only hypomorphs with reduced inhibition of p110, but also hypomorphs and dominant negative mutants that disrupt a novel regulatory role of p85α on PTEN or neomorphs that activate unexpected signaling pathways. The diverse phenotypic spectrum of these PIK3R1 driver mutations underscores the need for different treatment strategies targeting tumors harboring these mutations. This article describes the functional consequences of the spectrum of PIK3R1 driver mutations and therapeutic liabilities they may engender.
authors.affiliation: Department of Systems Biology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Lydia Wt
authors.initials: LW
authors.lastname: Cheung
authors.affiliation: Department of Systems Biology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.|Khalifa Bin Zayed Al Nahyan Institute of Personalized Cancer Therapy, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Gordon B
authors.initials: GB
authors.lastname: Mills
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D058543:Class Ia Phosphatidylinositol 3-Kinase; D006801:Humans; D009154:Mutation; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics; D051059:PTEN Phosphohydrolase / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics* / Q000378:metabolism; D011485:Protein Binding; D055503:Protein Multimerization; D015398:Signal Transduction
chemical_list: D000970:Antineoplastic Agents; D058543:Class Ia Phosphatidylinositol 3-Kinase; D051059:PTEN Phosphohydrolase; D019869:Phosphatidylinositol 3-Kinases; C588001:PIK3R1 protein, human
keywords: MAPK; PI3K; PIK3R1; mutation; p85; targeted therapy