Experimental Drug inhibits cell signaling Pathway and slows ovarian cancer growth In preclinical models

An experimental drug which is a crucial two points of cancer cell signaling pathway inhibits the growth of ovarian cancer cells and significantly increases survival in a mouse model of ovarian cancer blocks, a study at UCLA Jonsson Comprehensive Cancer Center has found.

The drug, called NVP-BEZ235, also inhibit the growth of ovarian cancer cells that have become resistant to conventional treatment with platinum chemotherapy, and helps to re-sensitize the cancer cells therapy. It also improves the effect of platinum chemotherapy on ovarian cancer cells that respond to the therapy, "said Dr. Oliver Dorigo, an assistant professor in obstetrics and gynaecology, Jonsson Cancer Center researchers and senior author of the study.

"Platinum-based chemotherapy drugs are effective in treating ovarian cancer as long as the cancer cells susceptible to platinum," said Dorigo. "But once the tumour is resistant, treatment of cancer is very challenging. This is an important clinical problem, since the majority of ovarian cancer patients resistance at some point during the treatment. Chemotherapy resistance to break is a difficult challenge, but essential if we want long-term survival for our patients improve. "

The study, conducted on cells lines and mouse models, appears in the issue of the journal of clinical cancer research, April 15, 2011.

Dorigo is working in his laboratory in recent years in an attempt to new therapies for ovarian cancer. Approximately 22,000 American women are diagnosed with ovarian cancer, and more than 14,000 deaths are attributed to this disease each year. Dorigo his research efforts focused on a road called PI3Kinase/Akt/mTOR, which once activated ovarian cancer growth. The activated process also makes the more aggressive and more likely to spread to other organs, Dorigo said, cancer so focused on offers great promise for more effective treatments for the disease.

In these two years of study, Dorigo and postdoctoral Chintda Santiskulvong found that inhibition of two control points of the road-PI3Kinase and mTOR-with NVP-BEZ235, cancer growth, both in cell culture dishes such as in mice with ovarian cancer declined. Also significantly increased survival in the mice, he said. More importantly, NVP-BEZ235 delayed growth of the ovarian cancer cells that had become resistant to platinum and helped to break that resistance.

"We were very encouraged to find that the NPT-BEZ235 ovarian cancer cells standard platinum treatment could re-sensitize," said Dorigo. "Furthermore, we found this drug to be more effective in cell growth inhibition of ovarian cancer than other drugs that target only one checkpoint, mTOR, in this process. We believe that NVP-BEZ235 superior efficacy because of the double effect on PI3Kinase and mTOR. "

The experimental drug is being tested as a single agent on the Jonsson Cancer Center in human clinical trials against other solid tumors. Researchers involved in these studies have said early results are encouraging.

"This is clearly a promising agent with activity in humans," said Dr. John Glaspy, a professor of Hematology/Oncology and a Jonsson Cancer Center scientist involved in the studies. "Still we assess the tolerability in patients."

Dorigo said that he hopes to a clinical trial for women with ovarian cancer that checks whether the combination of NVP-BEZ235 with Platinum chemotherapy, as he believes that the combination is more effective than each drug alone could be. .

The study was funded by the Ovarian Cancer Research Foundation/Liz Tilberis fair, the Gynecologic Cancer Foundation/Florence & Marshall Schwid ovarian cancer Award, a STOP cancer Career Development Award and the national institutes of health women's reproductive health Research Program.

Source:
UCLA's Jonsson Comprehensive Cancer Center