The impact of heterogeneity in phosphoinositide 3-kinase pathway in human cancer and possible therapeutic treatments

Phosphatidylinositol 3-kinase catalytic subunit alpha (PIK3CA) plays a crucial role in the initiation and progress of cancerous tumors through the overexpression of the PI3 K pathway promoting uncontrollable levels of cell proliferation. In addition only Class I PI3K has been discovered to be involved in human cancer due to its unique ability to produce phosphoinositide 3,4,5 trisphosphate (PIP3), which has been discovered to play a crucial role in human oncogenesis. The role of PIK3CA is lucubrated in breast cancer and gastric cancer, but is not well characterized in lung diseases. In this review, we summarized the common biology and mutations in PIK3CA with its related signaling pathways. Furthermore, we elucidated the PIK3CA heterogeneity in different domains, between various cancers and in different lung cancers. We also take a look at current inhibitors such as KP-372-1 (KP-1), KP-372-2 (KP-2), GSK690693, etc. in order to highlight potential treatment of PIK3CA mutations in human cancer and what directions future research should focus on. (C) 2016 Elsevier Ltd. All rights reserved.