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2025 Andrea & Steve Wynn – PCF Young Investigator Award

Roles, Regulations, and Therapeutic Potential of the Lysine Acetoacetylome in Prostate Cancer

Zhipeng Wang, PhD
University of Miami 

Mentors: Nima Sharifi; Phil Cole

Description:

  • Prostate cancer, particularly castration-resistant prostate cancer (CRPC), remains a major cause of cancer-related deaths, and more effective treatments remain urgently needed. Ketogenesis, induced by fasting, exercise, and a ketogenic diet, appears to sensitize some cancers to treatment by exploiting the reprogrammed metabolism of cancer cells. A key enzymatic pathway activated by ketogenesis is lysine acetoacetylation (Kacac), a protein modification activated by ketogenesis, with a possible role in cancer biology.
  • Dr. Zhipeng Wang hypothesizes that ketogenesis can influence cancer metabolism by acting on Kacac modifications, and that negative regulators of Kacac may have potential as new therapeutic targets.
  • In this project, Dr. Wang will investigate the functional significance, regulatory mechanisms, and therapeutic potential of altering Kacac in prostate cancer. He will identify Kacac-modified proteins, characterize their biological roles in prostate cancer metabolism, disease progression, and therapy resistance. Additionally, he will identify the enzymes responsible for “erasing” Kacac modifications and determine their potential as novel therapeutic targets.
  • If successful, this project will lead to new therapeutic approaches for patients with CRPC, including targeted inhibitors of Kacac regulatory enzymes as well as dietary strategies to modulate tumor metabolism. By identifying new drug targets and treatment pathways, this work has the potential to improve long-term outcomes for patients who no longer respond to standard therapies.

What this means to patients: Ketogenesis may have benefits in treating prostate cancer, but its effects on cellular biology and metabolism are not well understood. Dr. Wang’s project will define the mechanisms regulating ketogenesis and Kacac pathways in prostate cancer, providing new insights into prostate cancer biology and potential therapeutic approaches. This could provide a foundation for new metabolism-targeted cancer treatments.