Yaara Oren, Ph.D
Broad Institute
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
Summary:
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.