Remi Buisson, PhD
- Massachusetts General Hospital
Unraveling the role of ATR in DNA repair and ovarian cancer therapy
Proteins involved in the surveillance of genomic integrity, including BRCA1, BRCA2, and PALB2, help detect damage to DNA in cells and ensure that repairs are made when needed. Cells with mutations in BRCA1, BRCA2, and PALB2 have been associated with a heightened lifetime risk for ovarian cancer development and are extremely sensitive to inhibitors of the DNA repair protein PARP. These PARP inhibitors have recently emerged as promising anti-cancer drugs. However, mutations in BRCA genes and PALB2 account only for 15-20% of ovarian cancer. Dr. Buisson’s project will hone in on inhibitors of ATR kinase, a key protein regulating DNA damage signaling and DNA repair, as a way of rendering the other 80-85% of ovarian cancers sensitive to PARP inhibitors and other chemotherapeutics.
Mark Eckert, PhD
- University of Chicago
Targeting T-LAK cell-originated protein kinase (TOPK) for ovarian cancer therapy
Ovarian cancer is one of the most lethal cancers due to a lack of effective therapies. Dr. Eckert’s lab recently found that the protein T-LAK cell-originated protein kinase (TOPK) is expressed in ovarian cancer cells, but not most normal tissues. TOPK has roles in multiple cellular processes including DNA damage response, cell division, and metastasis. Excitingly, a small molecule inhibitor of TOPK was recently developed that has minimal toxicity to normal cells but effectively kills TOPK-expressing ovarian cancer cells, including cells from ovarian cancer patients. Dr. Eckert’s project will investigate the biological roles of TOPK in regulating ovarian cancer progression and directly test the efficacy and safety of TOPK inhibitors in patient samples and models of ovarian cancer.
Benjamin Izar, MD, PhD
- Dana-Farber Cancer Institute
Single-cell transcriptome analysis of treatment-resistant ovarian cancer and new strategies for drug discovery
Dr. Izar will be studying in fine detail the molecular changes that take place from the time that ovarian cancer cells respond to platinum chemotherapy to when they become resistant. He will employ an innovative genetic testing method to study ovarian cancer cells found in ascites (abdominal fluid) from ovarian cancer patients. This method takes single cells sloughed off from a tumor into ascites to evaluate all of the genes that are active at the moment that cancer cells become resistant. Looking at individual cells will allow Dr. Izar to see in great detail certain tumor sub-populations, including cancer stem cells, which are responsible for resistance over time. By understanding the mechanisms of treatment failure (resistance) that are invisible to other approaches, he will be able to generate new targets for therapy.
Elizabeth Poole, PhD
- Brigham and Women’s Hospital
- 2015 Skacel Family Scholar
Medication use and ovarian cancer survival
Although factors that contribute to ovarian cancer risk prior to diagnosis are currently being teased apart, factors which contribute to survival after a diagnosis of ovarian cancer have not yet been well studied. Dr. Poole’s project will develop the Nurses’ Health Study (two large prospective studies with over 30 years of follow up) to study factors that contribute to ovarian cancer survival including use of anti-inflammatory medications (e.g. aspirin and other non-steroidal anti-inflammatory drugs) and anti-stress medications (e.g. anti-depressants, beta blockers, anti-anxiety medications). Importantly, Dr. Poole has access to and will analyze information from women both before and after diagnosis, making this a unique project for identifying changes that women can make to their lifestyle to improve their survival.
Alexandra Snyder Charen, MD
- Sloan-Kettering Institute for Cancer Research
Chemotherapy, Somatic Mutations, and Neoantigens in Ovarian Cancer
Immunotherapy is a new treatment that boosts a patient’s immune system to attack ovarian cancer cells. Dr. Synder Charen’s lab has already shown in melanoma that when a tumor has a large number of genetic abnormalities (mutations), the immune system can better “see” and attack the tumor cells. Ovarian cancer cells do not have as many mutations as melanoma cells, but undergoing chemotherapy can cause additional mutations in cancer cells. This study will address whether chemotherapy can cause changes in ovarian cancer cells that allow the immune system the ability to see and potentially attack the tumors. These results will guide future strategies for giving immunotherapy in more effective ways.