Phosphoinositide 3-Kinase (PI3k) Inhibitors: Emerging target therapies against Cancer

Phosphoinositide 3-kinases (PI3Ks) were discovered in 1980, and since then drug developers have accelerated their research funds in order to find potential drug candidate for inhibiting PI3Ks for the treatment of cancers. Phosphatidylinositol 3-kinases (PI3Ks) are lipid kinases that act as intermediate signaling molecules in PI3K/AKT/mTOR signaling pathway. They are the key molecules that play central role in regulation of several cellular processes such as proliferation, adhesion, survival, and motility.

Mutation in these genes causes dysregulation of PI3K, which causes resistance to conventional therapies including biologics, hormonal therapy, tyrosine kinase inhibitors, radiation, and cytotoxics in breast cancer, glioblastoma, and non-small cell lung cancer. Latest research led by a scientific team at Beth Israel Deaconess Medical Center (BIDMC) demonstrates that “PI3K is a master regulator integrating a cancer cell’s architecture and its metabolism”. The study infers that cancer cells highly rely on the metabolism of sugar for their self-renewal as it not only generates energy but also biomass and PI3K inhibitors can inhibit the glucose breakdown.

Over the last 26 years, PI3K has been one of the most attractive molecular targets for cancer. Idelalisib is the first-in-class PI3Kδ-selective small-molecule inhibitor that has been approved by the FDA for the treatment of chronic lymphocytic leukemia, indolent B-cell non-Hodgkin’s lymphoma and relapsed small lymphocytic lymphoma. There are many drugs in pipeline such as TGR-1202, Alpelisib, Taselisib etc. that are in highest stage of clinical development. Several leading drug developers such as GlaxoSmithKline, Novartis, Bayer, and Pfizer have progressed their lead compounds in clinical trials. More than 35 drugs are in different stages of drug development for different isoforms of PI3Ks.

Insight by:
Jyoti Kumari
Associate Analyst