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Physicians Update


Physicians Update

Spring 2011

New Advances Benefit Treatment Options for Ovarian Cancer


PU-Spring11-Ovarian Cancer ResearchAbout 22,000 women are diagnosed with ovarian cancer annually, and 15,000 succumb to the disease. A woman diagnosed with ovarian cancer today has an overall 45-percent chance to survive five years. However, at advanced stages, the likelihood of survival is significantly lower, and approximately twothirds of all newly diagnosed cases of ovarian cancer are advanced.

“We have effective chemotherapies that we have used for more than 20 years to treat ovarian cancer,” says UCLA gynecologic oncologist Oliver Dorigo, M.D., Ph.D. “We can prolong the survival of patients with continuous treatment using these agents, but the problem arises when the tumor becomes resistant to these drugs. In addition, standard chemotherapeutic agents can have major side effects and impact on a patient’s quality of life. We are therefore working on developing more advanced therapies that take advantage of our understanding of the molecular biology of ovarian cancer.”

Using human ovarian cancer tissue, panels of cell lines and animal models, UCLA researchers are focused on investigating novel therapies that will attack ovarian cancer cells without harming the rest of the body. Dr. Dorigo and his research team recently published findings demonstrating promising effects of a novel drug in models for ovarian cancer that blocks important growth signals in ovarian cancer cells. This drug specifically inhibits two growth-promoting proteins, phosphoinositide 3-kinase and mTOR, and was even effective in cells resistant to standard platinum chemotherapy.

“We are focused on developing therapies based on our current knowledge of how ovarian cancer grows. However, to date, we’re still not even sure how this disease develops,” Dr. Dorigo explains.

At UCLA, a major effort of the research aims at understanding the interplay between the immune system of a woman and ovarian cancer. In particular, recent evidence points out that a group of specialized inflammatory cells called tumor-associated macrophages (TAMs) are actually encouraging the aggressive behavior of ovarian cancer rather than rejecting cancer.

“We know that cancer is immunogenic, which means the body sees cancer as a foreign insult. We are trying to build models that can mimic the disease to aid our understanding of how the bad inflammatory cells may be preventing cancer cells from being recognized by the good tumor-rejecting immune cells,” explains Lily Wu, M.D., Ph.D., associate director of the Institute for Molecular Medicine (IMED) at UCLA. According to Dr. Wu, she and Dr. Dorigo have successfully established immuno-competent mouse models of ovarian cancer that can be used to characterize immune cells, with the goal of being able to investigate therapies to specifically block TAMs.

“If we can understand the nature of the inflammatory cells in ovarian cancer, we can develop more effective treatments and even improve the supportive care for this disease,” she says. Recently, Dr. Wu, in collaboration with Dr. Dorigo, identified a promising way to block TAMs using an oral drug. Blocking these bad inflammatory cells might reduce ascites, the abnormal accumulation of fluid within the abdominal cavity, and support other immune cells in attacking ovarian cancer.

UCLA research teams are taking their novel treatment strategies from the bench to the bedside and offer participation in various, innovative clinical trials. Antoni Ribas, M.D., from the UCLA Department of Medical Oncology and Jonsson Comprehensive Cancer Center, has developed techniques that allow the genetically re-engineering of the patient’s immune effector cells. These modified immune cells are subsequently reinfused into patients in an effort to specifically target cancer cells. Efforts are underway to use this treatment strategy in patients with ovarian cancer. Other trials in patients with ovarian cancer investigate the effect of antibodies against the folate receptor or insulin-growth-factor receptor. Both these proteins are highly expressed on ovarian-cancer cells and therefore present a therapeutic target.

PU-Spring2011-Dr Dorigo“The future of ovarian cancer treatment will be based on understanding and exploiting the molecular and genetic makeup of ovarian cancer,” Dr. Dorigo says. “Ten years ago, we had very few drugs available for treatment of ovarian cancer. Today, the medical treatment options include many more agents, and the number is growing constantly. In the not so distant future, treatment of ovarian cancer will be customized for every patient based on the specific characteristics of the tumor tissue.”

Dr. Dorigo emphasizes that researchers at UCLA are actively pursuing various other aspects of ovarian cancer research, including the discovery of novel biomarkers, imaging technologies and ovarian cancer stem cells. “We don’t have reliable tests for detecting ovarian cancer early, in particular before it spreads beyond the ovaries,” Dr. Dorigo says.

Current blood tests and imaging technologies, such as ultrasound, are not sensitive enough to detect early stage disease. Focused efforts are underway at UCLA to identify proteins in the bloodstream (proteomics) and to analyze the genetic makeup of tumors (genomics) with the goal of developing a panel of biomarkers that provides reliable information to predict risk and detect the disease at earlier stages.

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