2022 John Miller – PCF Young Investigator Award
Targeting Metabolic Adaptation to Treat TP53-mutated Lethal Prostate Cancer
Young Yoo, PhD
Northwestern University
Mentors: Sarki Abdulkadir, MD, PhD, Navdeep Chandel, PhD
Description:
- Mutations in the TP53 gene are one of the most common drivers of cancer, including prostate cancer, making it an attractive therapeutic target. However, to date there are no effective treatments that specifically target tumors with TP53 mutations. Thus, identifying and targeting the Achilles heel of these cancers remain urgently needed.
- Dr. Young Yoo has found that TP53-mutated castration-resistant prostate cancer (CRPC) exhibit high levels of asparagine production, and are sensitive to treatments that limit asparagine bioavailability.
- In this project, Dr. Yoo will investigate the mechanisms by which different types of TP53 mutations control asparagine biosynthesis and how this alters prostate cancer cell metabolism.
- The role of asparagine metabolism in the development of resistance to hormonal therapy and progression to the CRPC state will be determined.
- Strategies to target asparagine production as a potential treatment option will be investigated in preclinical CRPC models.
- If successful, this project will provide insight into the functions of mutant TP53 and asparagine-mediated metabolic reprogramming in the development of CRPC, offering rationale for targeting this pathway as a new avenue to treat lethal prostate cancers with mutant TP53.
What this means to patients: New strategies are needed to prevent and treat CRPC. Dr. Yoo’s project will determine the mechanisms by which TP53 mutations increase asparagine levels and alter tumor metabolism to drive CRPC, and provide preclinical rationale for therapeutically targeting these altered metabolic pathways. As the safety and clinical efficacy of drugs targeting asparagine metabolism are currently being tested in clinical trials, these studies may accelerate clinical testing of such treatments in patients with CRPC.