The PIK3CA gene is important for human health, particularly its connection to diseases. Alterations within it can affect cellular processes, providing insights into disease development and potential therapies.
The PIK3CA Gene Explained
The PIK3CA gene provides instructions for creating the p110 alpha (p110α) protein, a component of the enzyme phosphatidylinositol 3-kinase (PI3K). This p110α protein functions as the catalytic subunit of the PI3K enzyme. The PIK3CA gene is located on chromosome 3, at position 3q26.32.
The PI3K enzyme is expressed throughout the body and localizes within the cytoplasm of cells. Its normal function involves adding a phosphate group to other proteins through phosphorylation. This enzyme plays a role in various cellular functions, including cell growth, proliferation, differentiation, motility, survival, and intracellular trafficking.
PIK3CA’s Role in Cancer
Mutations in the PIK3CA gene are observed in various human cancers, establishing it as an oncogene. These somatic mutations lead to an altered p110α protein, causing the PI3K enzyme to become abnormally active. This unregulated signaling promotes continuous cell growth and division, contributing to tumor formation.
PIK3CA mutations are common genetic alterations found in solid tumors. For instance, these mutations are found in 25-30% of breast cancers, 20-30% of endometrial cancers, and 15-20% of colorectal cancers. Other cancers such as ovarian, lung, and gastric cancers also show PIK3CA mutations. Over 80% of these mutations cluster at specific “hotspot” sites, particularly glutamates (E) 542 and 545 in the helical domain and histidine (H) 1047 in the kinase domain, which affect enzymatic activation.
Targeted Therapies for PIK3CA Mutations
The discovery of PIK3CA mutations led to the development of targeted therapies to inhibit the hyperactive PI3K pathway. Alpelisib (marketed as Piqray) is a PI3K inhibitor approved for certain advanced breast cancers with PIK3CA mutations. This drug selectively targets and inhibits the p110α subunit of PI3K, blocking uncontrolled signaling that drives cancer cell growth and survival.
Alpelisib works by downregulating the PI3K/AKT/mTOR signaling pathway, which reduces cell proliferation and increases programmed cell death in cancer cells. It is approved for use in combination with fulvestrant for postmenopausal women and men with hormone receptor-positive, HER2-negative advanced or metastatic breast cancer that has progressed after hormonal therapy. Genetic testing, often using an FDA-approved companion diagnostic test like the therascreen PIK3CA RGQ PCR Kit, is necessary to identify eligible patients.
Resources and Research for PIK3CA in Virginia
Virginia offers various resources for cancer care and research, including institutions that focus on or offer therapies for PIK3CA-mutated cancers. Facilities like the University of Virginia Cancer Center provide advanced patient care and research-based treatment options. This center is recognized as Virginia’s first National Cancer Institute-designated Comprehensive Cancer Center.
Virginia Cancer Specialists, with multiple locations in Northern Virginia, conducts extensive oncology research, including over 200 active clinical trials. These trials offer early access to investigational cancer treatments for various cancer types and genetic mutations, including those related to PIK3CA. Patients in Virginia can access genetic counseling services through organizations such as Virginia Oncology Associates to understand their risk and guide treatment plans.