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2019 PCF Challenge Award

Targeting MYC in Prostate Cancer

Principal Investigators: Sarki Abdulkadir, MD, PhD (Northwestern University), Gary Schiltz, PhD (Northwestern University)

Co-Investigators: Debabrata Chakravarti, PhD (Northwestern University), Bin Zhang, MD (Northwestern University), Michael Burns, MD, PhD (Northwestern University)

Description:

  • The MYC proteins (c-MYC, L-MYC and N-MYC) are critical cancer-promoting genes that drive up to 70% of all cancers, including a significant proportion of prostate cancers.
  • Preclinical studies have suggested that MYC may be an effective treatment target in advanced prostate cancer. However, MYC has proved difficult to target, and there are currently no clinically viable small molecule MYC-inhibitors available.
  • Sarki Abdulkadir and team will develop new small molecule inhibitors for targeting MYC in prostate cancer.
  • The team has already developed a series of MYC inhibitors that have shown excellent pharmacokinetic, toxicological and anti-tumor activity profiles in MYC-driven models of prostate cancer and leukemia. In this project, the team will perform additional chemistry to create MYC-inhibitors with further improved potency, selectivity, pharmacokinetics, and safety, which can be tested in clinical trials.
  • The effect of MYC-inhibitors on MYC activity and prostate cancer cell growth will be determined using preclinical prostate cancer models.
  • The potential for combining MYC-inhibitors with other treatments such as AR-targeted therapy, platinum chemotherapy, and the AURKA inhibitor CD532, will be investigated in preclinical models.
  • Finally, the team will determine whether MYC-inhibitors can sensitize prostate cancer to treatment with checkpoint immunotherapy, and identify the mechanisms that contribute to synergy between these treatments.
  • If successful, this project will result in the development of a new class of MYC-targeting therapies that will be active in prostate cancer as well as many other types of cancers, and identify promising combination treatment strategies.

What this means to patients: The MYC genes are some of the most important drivers of prostate cancer and many other types of cancer, but effective drugs that can target these proteins have yet to be developed. Dr. Abdulkadir and team will develop a new class of MYC-inhibitors that will be ready for testing in clinical trials and will identify combination treatment strategies for further increasing the efficacy of these new drugs.