Identification of Alpelisib (BYL 719) as a Potential Treatment for Endometrial Cancers
Analysis using human tumor explants identifies novel applications for a recently FDA-approved cancer drug
LONG BEACH, Calif., June 16, 2020 /PRNewswire/ -- Investigators at Nagourney Cancer Institute will report at the AACR Virtual Annual Meeting, June 22-24, that Alpelisib (BYL 719), an inhibitor of PI3Kα, that was recently approved for ER-Positive breast cancer in combination with Fulvestrant, may have an important role in the treatment of advanced uterine cancer as well as a number of other tumor types.
Endometrial cancers were found the most Alpelisib sensitive through the application of ex vivo analysis of programmed cell death (EVA/PCD), a laboratory platform that uses human-tumor-derived-3 dimensional tumor organoids to explore drug induced cytolysis, recreating in the laboratory the process of programmed cell death both apoptotic and non-apoptotic. The study compared Alpelisib activity in 388 patient-derived specimens isolated from surgical biopsies to examine disease-specific activity and found uterine cancers to be significantly more sensitive than other tumor types.
"The findings reveal an opportunity to explore the clinical utility of new drugs and drug combinations allowing clinical investigators to focus upon the most promising disease candidates," said Dr. Robert Nagourney, Founder and Medical Director of the Nagourney Cancer Institute. "Primary culture analyses like the EVA-PCD provide a window onto human tumor biology that offers the opportunity for better patient selection and more rapid and efficient drug development."
Up to 90 percent of endometrial carcinomas harbor molecular aberrations in PIK3- PTEN-AKT-mTOR pathway, while 40 percent of ER-Positive breast and 10-20 percent of colon cancers have activating mutations PIK3CA. The EVA/PCD results confirm these alterations to be therapeutic targets for Alpelisib with these PIK3CA-related tumors proving to be the most sensitive.
Additional analyses compared the activity of Alpelisib with other classes of drugs and explored novel drug combinations for activity and synergy.
"With the cost to bring a new drug to market today at over $1 billion, clinically validated laboratory platforms like the EVA/PCD technology have the capacity to streamline drug development, curtail costs and shorten the time from discovery to FDA approval," said Dr. Nagourney, noting that his results identify several interesting future options for Alpelisib.
EVA/PCD tumor primary culture analyses offer insights into drug actions that can be exploited for patient selection and drug discovery. By capturing cellular response to injury at the functional level, it can interrogate all mechanisms of drug resistance acting in-concert to reveal the complexity, redundancy and promiscuity of human tumor signal transduction pathways.
Uterine cancer is the most common gynecologic malignancy in the U.S. with over 65,000 new cases and 12,000 deaths each year. Caught early it can be cured with surgery, but the treatment of advanced disease remains an unmet need in contemporary medical oncology.
About the Nagourney Cancer Institute
The Nagourney Cancer Institute is a clinical research center that has pioneered the study of human tumor tissue for individualized cancer patient drug selection and has facilitated cancer drug discovery. Visit www.nagourneycancerinstitute.com for more information.
SOURCE Nagourney Cancer Institute
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