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2021 Rob Heyvaert and Bart Heynen-PCF Young Investigator Award

The Impact of Body Composition on Resistance to Androgen Signaling Inhibition (ASI) in Men with Localized High-Risk Prostate Cancer

Andrew Hahn, MD
The University of Texas MD Anderson Cancer Center

Mentors: Christopher Logothetis, MD, Daniel Frigo, PhD, Jennifer McQuade, MD

Description:

  • Men with localized high-risk prostate cancer have a 50% risk of recurrence, which is a major driver of deaths attributed to prostate cancer. In men with localized prostate cancer, body fat and obesity increase the risk for recurrence and lethal disease.
  • The influence of body fat on outcomes in advanced prostate cancer is less established, yet studies suggest that increased body fat may be associated with improved response to androgen receptor (AR)-targeted therapy in men with metastatic castration-resistant prostate cancer (mCRPC).
  • Considering the paradoxical association of body fat with outcomes in localized disease vs. mCRPC, it is critical to determine whether the influence of body fat on prostate cancer is driven by stage or by exposure to treatment with AR-targeted therapy.
  • Dr. Andrew Hahn will investigate the association between body fat and AR-targeted therapy in patients with localized high-risk prostate cancer who receive neoadjuvant AR-targeted therapy (prior to prostatectomy).
  • In this project, Dr. Hahn will use data and samples from several clinical trials of neoadjuvant AR-targeted therapy in localized high-risk prostate cancer patients that have tumor tissue and imaging available.
  • The phenotypes of different adipose tissue types in men with localized high-risk prostate cancer before and after AR-targeted therapy will be characterized.
  • Whether baseline or AR-targeted therapy-induced changes in adiposity and/or muscle measurements are associated with resistance to AR-targeted therapy will be investigated.
  • Biological links between body fat at baseline and after AR-targeted therapy and steroid hormone signaling in localized high-risk prostate cancer will be investigated.
  • If successful, this project will determine the biological interactions between body fat and treatment outcomes across prostate cancer disease states and identify whether body fat measurements may act as biomarkers to predict resistance to neoadjuvant AR-targeted therapy, thereby improving patient selection for this vs. alternative treatments.

What this means to patients: Obesity is associated with worse outcomes in patients with localized prostate cancer, but with improved responses to AR-targeted therapy in patients with mCRPC. Dr. Hahn will unravel this paradoxical observation by studying the impact of obesity on responses to neoadjuvant AR-targeted therapy in localized prostate cancer. This work will lead to new biomarkers to improve treatment selection and may empower patients by helping them understand how lifestyle influences prostate cancer.