Targeting the Phosphatidylinositol-3-kinase Pathway in Gastric Cancer: Can Omics Improve Outcomes?

• Published in: International neurourology journal Vol. 20; no. Suppl 2; pp. S131 - 140
• Main Authors: Tran, Phu, Nguyen, Cham, Klempner, Samuel J
• Format: Journal Article
• Language: English
• Published: Korea (South) Korean Continence Society 01-11-2016; 대한배뇨장애요실금학회
• Subjects: AKT oncogene protein; Clinical Trial; Molecular Targeted Therapies; mTOR protein; PIK3CA portein; Review; Stomach Neoplasms; 비뇨기과학; mTOR protein; Molecular Targeted Therapies; Clinical Trial; Stomach Neoplasms; AKT oncogene protein; PIK3CA portein
• ISSN: 2093-4777; 2093-6931; 2093-6931
• DOI: 10.5213/inj.1632740.370

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.