title: Targeting the Phosphatidylinositol-3-kinase Pathway in Gastric Cancer: Can Omics Improve Outcomes?
abstract: Phosphatidylinositol-3-kinase (PI3K) pathway signaling is an established oncogenic signal transduction pathway implicated in multiple malignancies. Therapeutic targeting of PI3K pathway components has improved outcomes in chronic lymphocytic leukemia, kidney cancer, breast cancer, and neuroendocrine tumors. Gastric cancers harbor some of the highest rates of oncogenic alterations in PI3K but attempts to translate this genomic observation have met with limited clinical success and novel approaches are needed. In the following review we discuss PI3K signaling, previous preclinical and clinical investigations in gastric cancer, and discuss future strategies aimed at overcoming resistance and improving efficacy. Identification and refinement of molecular tumor subtypes, development of predictive biomarkers along, and rational drug combination strategies are key to capitalizing on the therapeutic potential of PI3K pathway directed therapies in gastric cancers.
authors.affiliation: Division of Hematology-Oncology, University of California Irvine, Orange, CA, USA.
authors.forename: Phu
authors.initials: P
authors.lastname: Tran
authors.affiliation: Department of Pharmacy, University of California Irvine, Orange, CA, USA.
authors.forename: Cham
authors.initials: C
authors.lastname: Nguyen
authors.affiliation: The Angeles Clinic and Research Institute, Los Angeles, CA, USA.|Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
authors.forename: Samuel J
authors.identifier: 0000-0002-4062-0808
authors.initials: SJ
authors.lastname: Klempner
keywords: AKT oncogene protein; Clinical Trial; Molecular Targeted Therapies; PIK3CA portein; Stomach Neoplasms; mTOR protein