Ovarian cancer

Ovarian cancer program

Ovarian cancer of epithelial origin occurs in 70% - 80% of the cases whereas the vast majority of the remaining cases consist of germ line or stromal tumors. There is no single cause of epithelial ovarian cancer, but studies have suggested that certain factors appear to increase the risk of developing it. Some of these include age – particularly between 40 and 80, a family history of ovarian cancer or breast cancer (mutations in BRCA1 or BRCA2 genes), and hormone replacement therapy (HRT). Research also suggests that the use of fertility drugs and the combination of early menstruation and late menopause, which increases the number of menstrual cycles over a lifetime, may increase a women’s risk of ovarian cancer. Current treatments for ovarian cancer often include a combination of surgery, radiation therapy, and/or chemotherapy. These treatments have contributed to slight increases in overall survival rates in patients but there still exists large unmet medical needs for this disease. For example, current early diagnostic tools are unavailable due to the lack of early stage markers and there are very few ovarian cancer-specific therapeutic targets.

Alethia’s target discovery program in ovarian cancer is based on the use of an integrated platform developed developed by Alethia scientists. This approach combined the STAR technology, bioinformatics, and the silencing of candidate genes in cell-based models of ovarian cancer developed by our collaborators at CHUM in Montreal.

New strategies to treat ovarian cancer

Following the complete analysis of over 5000 sequences, a list of over 300 genes was selected for exhaustive tissue profiling analysis. These experiments revealed that 49 candidate genes were highly specific to ovarian tumors but conversely, their expression low or absent in most normal human tissues. These candidates include a few previously identified ovarian cancer markers but the vast majority of the genes encode proteins that have not been previously characterized in ovarian cancer which have unknown or predicted functions. Importantly, 35% of the sequences encode secreted or membrane-bound proteins against which monoclonal antibodies can be developed. Currently, Alethia is evaluating a number of monoclonal antibody candidates against these targets which is fueling the Company’s mAb pipeline.

New diagnostic possibilities

Ovarian cancer is a terrible disease that affects greater than 1 in 70 women in North America. Unfortunately, ovarian cancer is rarely diagnosed in its early stages and it is usually quite advanced by the time diagnosis is made. The 5-year survival rate for all stages is only 35% to 38%. If, however, diagnosis is made early in the disease, 5-year survival rates can reach 90% to 98%. The most popular diagnostic test for ovarian cancer is for CA125, a protein found on the surface of ovarian cancer cells and some normal tissues. It has been associated with other cancer types but is most often found at high levels in ovarian cancer. However, CA125 can also be elevated in certain normal conditions such as menstruation, pregnancy, and pelvic inflammatory disease. Other factors that have been associated with ovarian cancer are elevated levels of CEA and genetic abnormalities such as mutations in BRCA-1 and BRCA-2. Clearly, there is a need for more sensitive and specific serum markers to be able to not only detect ovarian cancer, but also detect the disease at an early stage to maximize the benefits of therapy.

With the objective of improving the sensitivity and specificity of currently available markers as well as ameliorating early detection, Alethia entered into a collaborative agreement with Biosite in 2007. As part of this agreement, Biosite will use its proprietary technology to generate monoclonal antibodies against 14 selected ovarian cancer-specific candidates. The antibodies will be tested in the serum of patients to evaluated Alethia’s targets as diagnostic biomarkers for ovarian cancer. Testing of these new markers will commence in 2008. The availability of an improved diagnostic test for ovarian cancer would be very beneficial to patients, especially for early diagnosis, and could contribute to earlier intervention and ultimately, an increase in overall survival rates.

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