PIK3CA, encoding the catalytic subunit p110α of Class IA Phosphatidylinositol 3-kinases (PI3K), is crucial in regulating cell survival, growth, cell cycle, and metabolism. It functions via the activation of the mTOR1-AKT pathway, a key signaling cascade involved in numerous biological processes [1,2].

Gain-of-function mutations in PIK3CA have been linked to a variety of disorders. Somatic activating mutations in PIK3CA are associated with vascular overgrowth syndromes, such as Klippel-Trenaunay syndrome, within the PIK3CA-related overgrowth spectrum (PROS). These mutations can lead to complications like thromboembolic events and orthopedic issues due to asymmetric overgrowth [1]. In cancer, PIK3CA mutations are prevalent, associated with resistance to first-line treatment and low survival rates in malignancies like colorectal cancer. There is evidence that PIK3CA-mutated colorectal cancer patients may benefit from aspirin treatment, though the exact mechanisms remain unclear [2]. PIK3CA mutations in solid malignancies are associated with poor prognosis, and inhibitors of the PI3K/AKT/mTOR pathway are being investigated as potential therapies [3]. In endometrial cancer, PIK3CA mutations seem to negatively influence survival outcomes, especially in low-grade tumors [4].

In conclusion, PIK3CA is essential in regulating key cellular functions through the mTOR1-AKT pathway. Research on PIK3CA-related disorders, especially those involving its mutations, has significant implications for understanding the pathogenesis of vascular overgrowth syndromes and various cancers. The study of PIK3CA provides potential therapeutic targets for these disease areas, highlighting the importance of further functional studies and in vivo research models such as KO/CKO mouse models to better elucidate its role in health and disease.

References:

1. Hughes, Meagan, Hao, Michelle, Luu, Minnelly. . PIK3CA vascular overgrowth syndromes: an update. In Current opinion in pediatrics, 32, 539-546. doi:10.1097/MOP.0000000000000923. https://pubmed.ncbi.nlm.nih.gov/32692051/

2. Hall, Daniella C N, Benndorf, Ralf A. 2022. Aspirin sensitivity of PIK3CA-mutated Colorectal Cancer: potential mechanisms revisited. In Cellular and molecular life sciences : CMLS, 79, 393. doi:10.1007/s00018-022-04430-y. https://pubmed.ncbi.nlm.nih.gov/35780223/

3. Willis, Owen, Choucair, Khalil, Alloghbi, Abdurahman, Dworkin, Lance, Nemunaitis, John. 2020. PIK3CA gene aberrancy and role in targeted therapy of solid malignancies. In Cancer gene therapy, 27, 634-644. doi:10.1038/s41417-020-0164-0. https://pubmed.ncbi.nlm.nih.gov/31988478/

4. Bredin, Hanna K, Krakstad, Camilla, Hoivik, Erling A. 2023. PIK3CA mutations and their impact on survival outcomes of patients with endometrial cancer: A systematic review and meta-analysis. In PloS one, 18, e0283203. doi:10.1371/journal.pone.0283203. https://pubmed.ncbi.nlm.nih.gov/36943861/