PI3 Kinase Inhibitor Zytiga Combo

Clinical trials are being carried out on the use of a PI3 kinase inhibitor in combination with Zytiga. PI3 kinase is involved in VEGFR stimulated angiogenesis and is involved in the growth of tumour metastases. PI3 kinase is also believed to mediate the resistance pathway and so a PI3 kinase inhibitor should help prevent Zytiga resistance. Salvestrols are natural inhibitors of the PI3 kinase pathway that have already been used in combination with Zytiga to combat resistance. The new drug PX-866 is a potent irreversible inhibitor of PI3 kinase and is currently undergoing Phase 2 clinical trials in comination with Zytiga and Prednisone.

Ongoing phase 2 trial of PX-866 in patients with recurrent or metastatic castration-resistant prostate cancer to include an additional group of up to 25 patients whose disease has begun to progress while receiving abiraterone (Zytiga) and prednisone.

PX-866 is a small molecule compound that is a Wortmanin analogue designed to inhibit the activity of phosphatidylinositol-3-kinase (PI3K), a component of an important cell survival signaling pathway.
PX-866 will be administered in addition to continuing treatment with Zytiga and prednisone. The primary endpoint of each part of this single-arm screening trial is the proportion of patients with lack of disease progression at 12 weeks from the initiation of therapy with PX-866.

PX-866 is an irreversible pan inhibitor of the PI3K/PTEN/AKT pathway, a critical cell signaling pathway that is activated in many types of human cancer. Aberrant activation and regulation of PI3K is implicated in a large proportion of human cancers, where it leads to increased proliferation and inhibition of apoptosis (programmed cell death). Natural inhibitors of PI3K such as salvestrols and wortmanin restimulate the cancer cells to undergo apoptosis.