Drug Shows Activity in Men with Advanced Prostate Cancer
News Apr 14, 2009
A new multi-center study shows that an experimental drug lowers prostate specific antigen (PSA) levels - a marker for tumor growth - in men with advanced prostate cancer for whom traditional treatment options have failed. The study, led by researchers at Memorial Sloan-Kettering Cancer Center (MSKCC), is published in Science Express, the online version of the journal Science.
“It's gratifying to know that our hypotheses about why men develop resistance to currently available treatments are confirmed and, most importantly, that there are already patients who are benefiting from our research, “ said Charles L. Sawyers, Chair of the Human Oncology and Pathogenesis Program at MSKCC and a Howard Hughes Medical Institute investigator.
Most men with metastatic prostate cancer eventually build up resistance to the drugs that lower or block male hormones and develop a more aggressive form of the illness called castration-resistant prostate cancer (CRPC), or hormone-refractory disease.
According to the study's findings, investigators studied two novel compounds, RD162 and MDV3100, and not only gained an understanding of their novel mechanism of action, but found that these agents showed activity in CRPC cells in culture and in mice.
The study also reports on a Phase 1/2 trial of MDV3100 in 30 patients with advanced CRPC and found that 22 out of 30 men showed declining PSA levels, and 13 out of 30 men (43 percent) had PSA levels fall by more than half.
Several years ago, the senior author of the study, Charles Sawyers, MD, and his colleagues at the University of California, Los Angeles (UCLA), uncovered a potential reason why metastatic prostate cancer patients eventually relapse with CRPC. This insight was used to discover RD162 and MDV3100.
"It's gratifying to know that our hypotheses about why men develop resistance to currently available treatments are confirmed and, most importantly, that there are already patients who are benefiting from our research," said Dr. Sawyers, Chair of the Human Oncology and Pathogenesis Program at MSKCC and a Howard Hughes Medical Institute investigator.
Current treatments for men who have advanced prostate cancers inhibit the activity of male hormones that help drive tumor growth. Many of these drugs disrupt the androgen (male hormone) receptor, which helps regulate cell proliferation, but tumors eventually become resistant to the drugs by expressing higher levels of the receptor. Preclinical studies by Dr. Sawyers and others have demonstrated that CRPC cells have increased expression of the androgen receptor and that overexpression of this receptor may contribute to the progression of disease.
Based on this information, Dr. Sawyers initiated a collaboration with Michael Jung, PhD, Professor of Chemistry at UCLA, that led to the discovery of a number of nonsteroidal, small molecule antiandrogen compounds, including MDV3100, which has been shown to retain its anticancer activity, even when the receptor's expression is elevated.
"The discovery and initial development of this drug was a collaborative effort all done in the academic setting, without reliance on the engine of the pharmaceutical industry that typically drives drug development," said Dr. Sawyers. Dr. Jung's group synthesized the compounds, which Dr. Sawyers' team then evaluated using prostate cancer mouse models engineered to highly express the androgen receptor, mimic progression to castration-resistant disease, and reflect the biology of clinical drug resistance.
PhoreMost Completes $15M (£11M) Series-A Round to Enter Drug DiscoveryNews
Investment to fund expansion of operations and progression of drug target pipeline.READ MORE
Computation and Chemistry Combine to Create World-First Auxetic ProteinNews
A team of chemists at the University of California, San Diego (UCSD) has now designed a two-dimensional protein crystal that toggles between states of varying porosity and density. This is a first in biomolecular design that combined experimental studies with computation done on supercomputers. The research, published in April 2018 in Nature Chemistry, could help create new materials for renewable energy, medicine, water purification, and more.
Fructose Formula Poses Risk to Babies With Metabolic DisorderNews
Babies with inherited intolerance of fructose face a risk of acute liver failure if they are fed certain widely available formulas containing fructose, pediatricians and geneticists are warning. Baby formula manufacturers should remove fructose or sucrose, or explicitly label their products to allow parents to avoid those sweeteners if necessary, the doctors say.
Comments | 0 ADD COMMENT
9th International Conference on Mass Spectrometry and Chromatography
Sep 21 - Sep 22, 2018