Fingerprinting drug resistance in ovarian cancer
by Robert Levy
Drs. Ursula Matulonis and John Quackenbush have teamed up to explore the genetic underpinnings of drug-resistant ovarian cancers.
Less common than other women's cancers, but generally more difficult to treat, ovarian cancer has attracted a relatively small share of research funding. As a result, knowledge of the molecular mayhem that occurs in malignant ovarian cells is a decade behind that of breast cancer, researchers estimate.
A new initiative by researchers and physicians in the Women's Cancers Program (WCP) at Dana-Farber may begin to close the gap. By combining knowledge acquired during a century of biomedical study and data from the latest gene-scanning equipment, investigators have the potential to vault ovarian cancer research far ahead of its current state.
The relatively low level of funding for ovarian cancer research is somewhat paradoxical given the disease's high toll. While 23,000 women are diagnosed with ovarian cancer every year in the United States (compared with about 178,500 new cases of breast cancer), more than 16,000 die of it annually, making it the most lethal gynecologic malignancy. To spur new advances against women's cancers, the WCP's Executive Council has recently created a Genetic Fingerprinting Research Fund for Breast and Ovarian Cancers with a $5 million fundraising goal. Among the most pressing issues is that most patients who respond to standard treatment – which includes platinum-based chemotherapy agents – relapse within a year or two. The key to better treatments is a deeper understanding of the disease and the genetic changes that influence whether a tumor is susceptible to platinum agents or is likely to become resistant to them.
Previous efforts to predict ovarian tumors' resistance to therapy by analyzing their patterns of gene activity have been somewhat unsatisfactory. This is partly because physicians have tended to treat all ovarian tumors alike, although there are at least four pathologic subtypes and early-stage tumors may be genetically distinct from advanced ones.
The Dana-Farber project takes account of this variability and delves into the genetics of the disease with a unique array of talent. The research team includes John Quackenbush, PhD, an expert in computational biology (the science of dealing with mammoth data sets); Ronny Drapkin, MD, PhD, who has developed a "living tissue bank" of ovarian tumors to study; and Ursula Matulonis, MD, director of medical gynecologic oncology at DFCI.
"Our aim is to identify the genetic fingerprints of platinum-resistant ovarian tumors, and contrast them with the fingerprints of platinumsensitive tumors," says Dr. Matulonis. "The next step is to develop a clinical test for determining which type a woman has, and how she should be treated. Ultimately, we hope to identify genes in platinum-resistant cancer that can be targeted by new drugs."
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