Chemo-Resistant Ovarian Cancer

(Ivanhoe Newswire) -- Ovarian cancer, a prevalent and malignant disease among women, is usually treated with chemotherapy. But what if the cancer becomes resistant to the treatment? New research shows that some cases of high-grade serous ovarian cancer can become chemoresistant.

David Bowtell, Ph.D., head of the Cancer Genomics and Genetic Program, and his colleagues found chemoresistance in women with high-grade serous cancer, a subtype of ovarian cancer. They believe this resistance is associated with the absence of the gene LRP1B, which encodes a member of a family of proteins to transport lipids into cells.

"We were interested in identifying the molecular changes that occurred in a tumor between the time when a woman first presented for surgery and chemotherapy, and the time when the tumor recurred and eventually became resistant to chemotherapy," Dr. Bowtell was quoted as saying.

In order to examine this, researchers took paired pretreatment and post-treatment tumor samples from each of their participants and analyzed metastatic lesions for spatial and temporal genomic variation, which are measures of how the tumors genetically evolve over time. Then, researchers compared the levels of genomic change among women who were initially chemosensitive to those who were resistant to chemotherapy from the beginning.

They found that tumors that were initially sensitive to chemotherapy later became resistant and evolved even further than tumors that were chemoresistant from the start.

"We were surprised by the extent of variation that was present among the tumor deposits collected at surgery, and by how far the tumors could evolve during therapy," Dr. Bowtell was quoted as saying. "The existence of multiple cancer genomes in an individual patient could provide many opportunities for the cancer to circumvent chemotherapy and may help explain why it has been so difficult to make progress with this disease."

"Many women with high-grade serous ovarian cancer experience an excellent response to initial chemotherapy, but unfortunately the disease often returns and becomes resistant to treatment," Bowtell was quoted as saying. "If we can comprehensively map the mechanisms that confer resistance, we may be able to predict whether some women are likely to respond to a certain drug or not, and find ways of reversing resistance."

This study forms part of an ongoing international collaboration effort, known as the International Cancer Genome Consortium (ICGC). Its purpose is to systematically map the emergence of chemotherapy resistance in ovarian cancer and other solid cancers. Dr. Bowtell believes this effort is needed and will be necessary in understanding why treatment failure occurs.

Source: American Association for Cancer Research, August 2012

Source: http://www.ivanhoe.com/channels/p_channelstory.cfm?storyid=29895

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