http://www.cancer.ucla.edu/On April 15, 2011, UCLA’s Jonsson Comprehensive Cancer Center released the results of a study, which evaluated a new drug for the treatment of ovarian cancer. The drug blocks two points of a crucial cancer cell signaling pathway that inhibits the growth of ovarian cancer cells and significantly increases survival in an ovarian cancer mouse model. The drug, called NVP-BEZ235, also inhibits growth of ovarian cancer cells that have become resistant to the conventional treatment with platinum chemotherapy. Furthermore, it helps to re-sensitize the cancer cells to the therapy and enhances the effect of platinum chemotherapy on ovarian cancer cells that are still responding to the therapy, said Dr. Oliver Dorigo, an assistant professor of obstetrics and gynecology, a Jonsson Cancer Center researchers and senior author of the study. He noted, “Platinum-based chemotherapy drugs are effective in treating ovarian cancers as long as the cancer cells remain sensitive to platinum.” He added, “Once the tumor becomes resistant, treating the cancer becomes very challenging. This is a significant clinical problem, since the majority of ovarian cancer patients develop resistance at some point during treatment. Breaking chemotherapy resistance is a difficult challenge, but crucial if we want to improve long-term survival for our patients.”
Approximately 22,000 American women are diagnosed with ovarian cancer, and more than 14,000 deaths are attributed to this disease every year. During the last several years, Dr. Dorigo has been working in his laboratory in an effort to develop new therapies for ovarian cancer. He has focused his research efforts on a pathway called PI3Kinase/Akt/mTOR, which once activated promotes ovarian cancer growth. The activated pathway also makes the cancer more aggressive and more likely to spread to other organs, Dorigo said, so targeting it offers great promise for more effective therapies for the disease. In this two-year study, Dorigo and postdoctoral fellow Chintda Santiskulvong found that inhibiting two checkpoints of the pathway (PI3Kinase and mTOR) with NVP-BEZ235 decreased cancer growth, both in cell culture dishes and in mice with ovarian cancer. It also significantly increased survival in the mice, he said. More importantly, NVP-BEZ235 slowed growth of the ovarian cancer cells that had become resistant to platinum and helped to break that resistance.
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