> Our Work > The Work We Fund

2019 PCF Challenge Award

Targeting the Translational Oncogenic Program Through eIF4E and eIF4A in Metastatic Castration Resistant Prostate Cancer Using Three Novel Small Molecule Inhibitors (eFT 508/Tomivosertib, eFT 2560, and eFT 226)

Principal Investigator: Hao Nguyen, MD, PhD (University of California, San Francisco)

Co-Investigators: Davide Ruggero, PhD (University of California, San Francisco), Peter Carroll, MD, MPH (University of California, San Francisco)

Description:

  • eIF4E is a protein that is required for gene expression and is necessary for life. Cancer cells also need this protein to maintain their survival, and typically boost its activity. Whether targeting eIF4E may be have therapeutic benefit in cancer needs to be studied.
  • Hao Nguyen and team have discovered that eIF4E is highly active in all stages of prostate cancer. The team will investigate its potential as a therapeutic target and the mechanisms by which it drives prostate cancer growth.
  • The team will test the efficacy of several small molecule inhibitors of eIF4E and its partner eIF4A in combinations with one another or with enzalutamide in a preclinical patient-derived prostate cancer models. The inhibitors to be tested include two developed by the team, and a third that was previously developed and is currently in a stage 2 clinical trial in advanced prostate cancer.
  • The mechanisms by which eIF4E/A drive prostate cancer growth and the effects of eIF4E/A-inhibition on prostate cancer gene expression will be determined.
  • Whether eIF4E levels or activity in prostate cancer samples can be used as biomarkers to select patients who are most likely to respond to eIF4E and eIF4A-targeted therapies will be determined.
  • The mechanisms by which prostate cancer cells develop resistance to eIF4E and eIF4A-targeted therapies will be determined.
  • If successful, this project will determine the biology by which eIF4E/A drive prostate cancer and lead to clinical trials for this new class of drugs.

What this means to patients: eIF4E is a protein that drives prostate cancer growth and progression. Dr. Nguyen and team will determine the biology by which eIF4E and its partner eIF4A drive cancer growth and will determine the therapeutic potential for targeting these proteins, which may lead to clinical trials for a new class of drugs that may impact all stages of prostate cancer.