Great article. Very informative…
Posted by on 01/18 at 04:01 PM
Illustration: Gianoapolo Pagni
New family of drugs offers hope for breast cancer patients
No one wants to hear that they have advanced cancer, but women facing metastatic breast cancer may soon have a new therapy option in their hard-pitched fight against the disease. City of Hope researchers and colleagues have shown that one of the first members of a new family of drugs appears to slow tumors’ progression in these women.
The drug is known as Vorinostat. In a phase II clinical trial, it stabilized cancer growth in a small group of women who recently were treated for stage 4 breast cancer. Stage 4 breast cancer is the most advanced stage of the disease and involves cancer spread to other organs.
The medication belongs to a family of drugs called histone deacetylase, or HDAC, inhibitors. These agents come from advances in the field of epigenetics, a relatively new line of research that studies how genes are inappropriately “turned on” or “off” without any changes in genetic sequences themselves.
Unlike other recent anticancer strategies that target altered genes and their gene products, epigenetic strategies seek to turn on genes that have been silenced — those genes that can help put the brakes on cancer.
The field of epigenetics can be traced back to early work carried out by Arthur Riggs, Ph.D., director of City of Hope’s Beckman Research Institute, and colleagues, said George Somlo, M.D., professor and director of breast oncology in the Division of Medical Oncology & Therapeutics Research and the study’s senior author.
In the Vorinostat study, participants took the drug in a pill form twice a day for two weeks, then took a week off. Overall, side effects were mild and the drug was well tolerated, said Somlo, who also co-directs the City of Hope Breast Cancer Program.
The drug stabilized tumor growth in four of the 14 women in the study. One woman remained on the drug for more than 13 months after beginning treatment. “She was going on cruises and traveling around the world,” said medical oncologist Thehang Luu, M.D., the study’s principle investigator.
“We hope that this and other HDAC inhibitors can provide a novel treatment option as part of combination therapy — especially for women with triple-negative breast cancers,” Luu said, referring to cancers that do not overexpress estrogen, progesterone or human epidermal growth factor (HER2) receptors. Luu believes HDAC inhibitors and other drugs emerging from epigenetics will likely work best when combined with drugs that battle cancer from several directions.
City of Hope investigators plan to join a phase II clinical trial for metastatic breast cancer patients that will test a combination of Vorinostat, bevacizumab (an agent targeting blood vessels that provide nourishment to cancer cells) and Paclitaxel, a chemotherapy drug, Somlo noted.
Researchers are investigating several HDAC inhibitors, including Belinostat (also called PXD101), currently offered in a phase II clinical trial for patients with mesothelioma and a phase I trial for patients with advanced solid tumors. And Vorinostat is in phase II clinical trials at City of Hope for two other cancers: nonHodgkin’s
lymphoma and bladder cancer.
The investigations come through the California Cancer Consortium, a National Cancer Institute-funded cooperative that unites City of Hope, the University of Southern California, UC Davis and the University of Pittsburgh to conduct small studies of up-and-coming drugs.
“Science is moving quickly on these therapies,” Luu said. “We’d like to be able to speed them to our patients as fast as we can.”
Alicia Di RadoThehand Luu and George Somlo
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