• What is PIK3CA?
  • PIK3CA in Lung Cancer
  • Clinical Trials


Phosphatidyl 3-kinases (PI3K) are a family of lipid kinases involved in many cellular processes, including cell growth, proliferation, differentiation, motility, and survival. PI3K is a heterodimer composed of 2 subunits—an 85 kDa regulatory subunit (p85) and a 110 kDa catalytic subunit. The PIK3CA gene encodes p110α, one of the catalytic subunits.

PI3K converts PI(4,5)P2 [Phosphatidylinositol 4,5-bisphosphate] to PI(3,4,5)P3 [Phosphatidylinositol (3,4,5)-trisphosphate] on the inner leaflet of the cell membrane. PI(3,4,5)P3 recruits important downstream signaling proteins, such as AKT, to the cell membrane resulting in increased activity of these proteins.

Mutant PIK3CA has been implicated in the pathogenesis of several cancers, including colon cancer, gliomas, gastric cancer, breast cancer, endometrial cancer, and lung cancer (COSMICSamuels et al. 2004)



Figure 1.
Schematic of the MAPK and PI3K pathways. . Growth factor binding to receptor tyrosine kinase results in activation of the MAPK signaling pathway (RAS-RAF-MEK-ERK) and the PI3K pathway (PI3K-AKT-mTOR). The letter "K" within the schema denotes the tyrosine kinase domain.

Related Pathways

Contributors: Leora Horn, M.D., M.Sc., William Pao, M.D., Ph.D. (through April 2014), Christine M. Lovly, M.D., Ph.D.

Suggested Citation: Horn, L., W. Pao, C. Lovly. 2015. PIK3CA. My Cancer Genome https://www.padiracinnovation.org/content/disease/lung-cancer/pik3ca/?tab=0 (Updated December 7).

Last Updated: December 7, 2015

PIK3CA in Non-Small Cell Lung Cancer (NSCLC)

Somatic mutations in PIK3CA have been found in 1–3% of all NSCLC (COSMICKawano et al. 2006; Samuels et al. 2004). These mutations usually occur within two "hotspot" areas within exon 9 (the helical domain) and exon 20 (the kinase domain). PIK3CA mutations appear to be more common in squamous cell histology compared to adenocarcinoma (Kawano et al. 2006) and occur in both never smokers and ever smokers. PIK3CA mutations can co-occur with EGFR mutations (Kawano et al. 2006; Sun et al. 2010). In addition, PIK3CA mutations have been detected in a small percentage (~5%) of EGFR-mutated lung cancers with acquired resistance to EGFR TKI therapy (Sequist et al. 2011).

Contributors: Christine M. Lovly, M.D., Ph.D., Leora Horn, M.D., M.Sc., William Pao, M.D., Ph.D. (through April 2014)

Suggested Citation: Lovly, C., L. Horn, W. Pao. 2015. PIK3CA in Non-Small Cell Lung Cancer (NSCLC). My Cancer Genome https://www.padiracinnovation.org/content/disease/lung-cancer/pik3ca/ (Updated June 18).

Last Updated: June 18, 2015

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