Recent progess in phosphoinositide 3-kinases: oncogenic properties and prognostic and therapeutic implications.
Phosphatidylinositol 3-kinases (PI3Ks) are a group of lipid kinases that coordinate various fundamental cellular responses including mitogenic signaling, cell survival and proliferation, vesicular trafficking, cytoskeletal rearrangement and metabolism. Overexpression caused by genetic alterations such as the amplification or gain of copy numbers was frequently observed for various PI3Ks in different human cancers. In recent years, the high-frequency somatic mutations of PIK3CA observed in different human cancers further strengthen the notion that PI3Ks are optimal targets for therapeutic intervention. In this review, I summarize current experimental evidence about the transformation capability and oncogenic properties of different PIK3CA mutations identified in human cancers. I also discuss the association of PIK3CA mutations with other genetic markers, as well as the prognostic value of PIK3CA somatic mutations in human cancers. Finally, I discuss the application of PI3Ks as therapeutic targets in human cancers, including targeted and combinational therapies and the potential challenges that confront their clinical applications.
Wu
Guojun
G
Barbara Ann Karmanos Cancer Institute, Department of Pathology, Wayne State University, HWCRC, Room 840.2, 4100 John R, Detroit, MI 48201, USA. wugu@karmanos.org
D000970:Antineoplastic Agents / Q000627:therapeutic use; D020022:Genetic Predisposition to Disease; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism; D009154:Mutation; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D051059:PTEN Phosphohydrolase / Q000378:metabolism; D058539:Phosphatidylinositol 3-Kinase / Q000235:genetics / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011379:Prognosis; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*
D000970:Antineoplastic Agents; D008565:Membrane Proteins; D000081082:Phosphoinositide-3 Kinase Inhibitors; D058539:Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt; C446603:TPTE protein, human; D051059:PTEN Phosphohydrolase