Mutations in PIK3CA
PIK3CA gene belongs to the PI3K (phosphoinositide 3 kinase) family and encodes the p110 catalytic subunit of PI3K. These lipid kinases promote various biological processes, including cell proliferation and survival. PIK3CA mutations have been identified in many hereditary syndromes and human solid tumors, including colon, breast, brain, ovary, liver and lung.
In colorectal cancer, mutations in PIK3CA are found in 10% to 20% of tumors, are associated with specific clinicopathological and molecular characteristics, such as the proximal location of the tumor, microsatellite instability (MSI) events, and K-RAS mutation. PIK3CA mutations activate PTEN-PI3K-AKT pathway, which is downstream of both the EGFR route and route RAS-RAF-MAPK. These PIK3CA mutations have been associated with poor prognosis in endometrial, breast and colorectal cancer. Mutations in exons 9 and 20 are associated with resistance to cetuximab in patients with colorectal cancer. Therefore, the profile of mutations in PIK3CA can effectively select patients most likely to respond positively to anti-EGFR immunotherapy.
In breast cancer, the presence of PIK3CA mutations is associated with a poorer pathologic complete response (pCR) to patients who received anti-HER2 therapy (trastuzumab, lapatinib, or a combination of the two).
