While many ovarian cancer patients initially respond to chemotherapy, most patients ultimately develop chemotherapy-resistant disease that is difficult to treat and confers a poor prognosis. Understanding the mechanisms by which ovarian cancer cells become chemotherapy resistant, and generating new ideas for treatment of chemotherapy-resistant cancer, is critical to improving patient outcomes. This project builds on our previous research in which we tested thousands of genes in ovarian cancer cells to identify genes that affect ovarian cancer cell survival after treatment with platinum and/or taxane chemotherapy. Several genes that inhibit cell death signaling pathways (apoptosis) were associated with chemotherapy resistance. Increasing levels of these anti-apoptotic proteins could promote ovarian cancer cell survival after chemotherapy treatment. On the other hand, we and others showed that inhibitors of anti-apoptotic proteins (essentially, drugs that block the proteins protecting cancer cells from death) can collaborate with chemotherapy to increase cancer cell killing.
Our current project will investigate the mechanisms by which chemotherapy and anti-apoptotic protein inhibitors cooperate to kill cancer cells more effectively. We will test ovarian cancer cell lines for sensitivity to anti-apoptotic protein inhibitors and identify potential biomarkers of response. Our project will test whether targeting anti-apoptotic proteins can increase the activity of chemotherapy or other drugs against ovarian cancer, and whether these inhibitors can help to more effectively treat drug-resistant ovarian cancer.