PIK3CA gene-Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha.
The PIK3CA gene provides instructions for making the p110 alpha (p110α) protein, which is a subunit of an enzyme called phosphatidylinositol 3-kinase (PI3K).
The p110α protein is called the catalytic subunit because it performs the action of PI3K.
Another subunit produced by a different gene regulates the enzyme’s activity.
As other kinases, PI3K adds a cluster of oxygen and a phosphate group to other proteins through phosphorylation.
PI3K phosphorylates certain signaling molecules, which triggers a series of additional reactions that transmit chemical signals within cells.
PI3K signaling is important for many cell activities: cell growth and division (proliferation), movement (migration) of cells, production of new proteins, transport of materials within cells, and cell survival.
PI3K signaling may be involved in the regulation of several hormones.
PI3K signaling plays a role in the maturation of adipocytes.
PI3K inhibitors approved for indications involving relapsed to refractory indolent non-Hodgkin lymphoma or chronic lymphocytic leukemia include idelalisib, copanlisib, duvelisib, and umbralisib.
These inhibitors work on the PI3K Delta isoform.
Alpelisib is approved for breast cancer and PIK3CA- related overgrowth spectrum.
Side effects of this drug class include fatal or serious infections, neutropenia, and immuno mediated toxic side effects such as diarrhea, colitis, hepatotoxicity, pneumonitis, and dermatological toxicity.
PI3K alpha isoform can cause hyperglycemia and hypertension.
Immune mediated toxicities A partly attributed to decreased regulatory T – cell activity.
As single agents serious adverse reactions have been observed and up to 65% of patients and severe adverse reactions in up to 85%.
Adverse side effects leads to dose interruptions, reductions come or permanent discontinuation of these agents.
Approximately 40% of hormone receptor positive and HER2 negative breast cancers harbor inactivating mutation in PIK3CA.
The gene product of PIK3CA is phosphatidylinositol 3 kinase a tyrosine kinase and key component of the PI3K and protein kinase B (AKT) pathway that regulated cell growth.
Dysregulation of the PI 3K and AKT pathway occurs in several subtypes of breast cancer, and maybe highest in triple negative breast cancer, buddy incidence of these mutations is most common in the hormone receptor positive and HER2 breast cancer.
PIK3 inhibitors include alpelisib, capivasertib and inavolisib.
In patients with PIK3CA mutated hormone receptor positive, HER2 negative locally advanced or metastatic breast cancer inavolisib plus palbociclib-fulvestrant led to longer progression free survival than placebo plus palbociclib-fulvestrant with a greater incidence of toxic effects.