Validation of CDK12 Inhibition in Osteosarcoma
Background
My project “Investigating the Therapeutic Potential of Combining CDK12 Inhibition with Standard Therapy in Osteosarcoma (OS)” focuses on investigating therapeutic potential of CDK12 inhibition using a covalent inhibitor of CDK12, E9, in OS cells. Over the past 11 months, I’ve collected data showing E9’s significant cytotoxic effects on OS cells as well as its promising effects of inducing apoptosis, cell cycle arrest and DNA damage.
Project Goal
This summer, I will investigate CDK12 inhibition with E9 in combination with conventional chemotherapy used in everyday practice to treat OS patients (Cisplatin, Doxyrubicin, Methotrexate) in hopes of increasing the efficacy of these agents in OS cells and observing a more profound cytotoxic effect on OS cells in comparison to a single agent treatment. Upon finding a higher efficacy combination treatment, I will measure its effect on apoptosis, DNA damage and cell cycle arrest. Successful completion of my research will not only contribute towards the preclinical value of CDK12 as a therapeutic strategy, but also improve on current standard treatments when utilized together in OS patients. Not only will this lead to critical clinical implementation of effective therapeutic strategies, but it will also provide groundbreaking knowledge about many cancers characterized by impaired DDR and genomic instability.
Mentored by Dr. Rani George
Dana-Farber Cancer Institute, Boston, MA
