Yasuto Kinose, M.D., Ph.D.
University of Pennsylvania
Philadelphia, PA, United States
2018 SKACEL FAMILY SCHOLAR
Project: Evaluation of a novel combination therapy in clear cell ovarian cancer orthotopic patient-derived xenograft models
Research Area: Novel Therapy, Cancer Biology
While clear cell ovarian cancer is a relatively rare subtype of ovarian cancer, it is also the most difficult to treat in advanced stages or when the cancer comes back. It’s been difficult to understand the biology of clear cell ovarian cancer and develop new treatment approaches because there are not enough model systems to study the disease. Dr. Kinose’s work addresses this vital need to identify more effective treatments for this type of ovarian cancer. Clear cell ovarian cancers demonstrate unique genetic mutations that effect the ability of cells to repair their DNA and other functions which are essential for cancer cell survival. Dr. Kinose and his colleagues have discovered a promising new combination using drugs known as WEE1 inhibitors and BET inhibitors that kill these cancer cells when used together. In this project, Dr. Kinose will develop this exciting new combination further by understanding how it works and confirm the findings in novel clear cell ovarian cancer mouse models developed from patient tumors. In these mouse models, pieces of tumors taken from patients can be implanted and grown prior to testing new therapies. The findings from this project may identify a new treatment for this aggressive type of ovarian cancer.
Yaara Oren, Ph.D
Cambridge, MA, United States
Project: Using a novel single-cell lineage tracing technique to uncover the mechanisms driving ovarian cancer recurrence
Research Area: Cancer Biology, Chemotherapy Resistance
Despite a good initial response to chemotherapy, ovarian cancer comes back in the majority of patients and leads to death within 5 years of diagnosis. When the cancer first comes back, it may still be responsive to chemotherapy in many cases before eventually becoming drug resistant. Several mechanisms have been suggested to contribute to the disease coming back but we don’t know exactly how and how much each of these mechanisms impact the process. There is also a need for better experimental models to understand the re-emergence of cancer which are currently lacking, making the development of new therapies that target this crucial stage of the disease difficult. Dr. Oren proposes to uncover and understand the factors that contribute to the re-emergence of ovarian cancer that is still responsive to chemotherapy, by using a new method that allows her to trace how individual single cells respond to multiple rounds of chemotherapy. Her novel tracing technique will allow her to study how an ovarian cancer cell’s past behavior and pedigree affect its ability to survive drug treatment. Dr. Oren will combine several techniques including microscopy, sequencing, mathematical modeling and patient data to expose not only what makes cells resistant to initial treatment but also what effects their ability to regenerate the tumor. This unique methodology will allow Dr. Oren to identify which genes and cellular pathways are important for relapse. The insights gained from this integrated approach will help devise new drug therapies that delay or even prevent the emergence of resistant ovarian cancer.