PIK3CA

The protein encoded by PIK3CA gene is the catalytic subunit of PI3Ks, a family of lipokinases that specifically phosphorylates the 3-hydroxyl group of phosphatidylinositol and produces second messenger inositol substances, such as PIP3, which can promote the transfer of AKT to the cell membrane and be activated by PDK1/PDK2. AKT is a core factor in the PI3K/AKT signaling pathway, and abnormal activation of AKT can lead to the occurrence of tumors. E542 hot spot mutation is located in the spiral domain of PIK3CA gene, experiments show that the cell line containing this mutation has similar cell proliferation ability and activity to the wild type. The mutation of PIK3CA gene can activate the PI3K signaling pathway, leading to the abnormal enhancement of the catalytic activity of PI3Ks and promoting the carcinogenesis of cells, which is associated with colorectal cancer, glioblastoma, gastric cancer, breast cancer and lung cancer (PMID: 24782230, PMID: 25533673, PMID: 15016963. PMID: 28528867).

In a preclinical study, taselisib, a small molecule PI3K inhibitor, was shown to be effective in treated patients with stage IV squamous cell lung cancer who carry PIK3CA mutations at codons 545th, 542nd and 1047th. In a clinical trial that patients with advanced non-small cell lung cancer, an AKT inhibitor MK-2206 was used to treat patients with PIK3CA mutations. In addition, copanlisib, a pan-PI3K inhibitor, has been approved by the FDA for the treatment of patients with relapsed follicular lymphoma who have undergone at least two prior systemic therapies. Alpelisib has shown tolerable safety and promising clinical activity in patients with PIK3CA modification. In a clinical trial, buparlisib plus fulvestrant take effect in postmenopausal women with hormone-receptor-positive, HER2-negative, advanced breast cancer (PMID: 28490463, PMID: 28779636, PMID: 29223745).