Pharmacy

Investigators at the University of California, Los Angeles worked with the experimental drug NVP-BEZ235. This drug is an imidazoquinoline derivative and Phosphoinositide 3-Kinase (PI3K) inhibitor that inhibits PI3K and mammalian Target of Rapamycin (mTOR) kinase activity by binding to the ATP-binding cleft of these enzymes. PI3K and mTOR are members of a molecular signaling pathway, which once activated promotes ovarian cancer growth. Tumours with this pathway are more aggressive and more likely to metastasize.

The   investigators   described   the drug's effect on cell proliferation in 18 ovarian cancer cell lines, including four pairs of  syngeneic  cisplatin-sensitive and cisplatin-resistant cell lines. They also evaluated the in vivo effects of NVP-BEZ235 on established tumour growth using an immunocompetent, transgenic murine ovarian cancer model. Results revealed that NVP-BEZ235 decreased cell proliferation in all ovarian cancer cell lines assayed and sensitized

Cisplatin-resistant cells to the cytotoxic effects of cisplatin. Oral administration of NVP-BEZ235 resulted in significantly longer survival of the mice with ovarian tumours compared to control animals that were not treated.