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2019 PCF Challenge Award

A Systematic Approach for Targeting WNT Signaling in Metastatic Prostate Cancer

Principal Investigators: Li Xin, PhD (University of Washington), Pete Nelson, MD, PhD (Fred Hutchinson Cancer Research Center), Calvin Kuo, MD, PhD (Stanford University)

Co-Investigators: Xing Wei, PhD (University of Washington), Eva Corey, PhD, (University of Washington), Colm Morrissey, PhD (University of Washington)

Description:

  • The WNT pathway is a fundamental growth control pathway that is important during development and for maintenance of stem cells, but can also drive cancer. WNT pathway mutations have been identified in ~18% of metastatic castration-resistant prostate cancer (mCRPC) cases. However, the role of the WNT pathway in prostate cancer and its potential as a therapeutic target is largely unknown.
  • Li Xin and team will investigate the biology of the WNT pathway in prostate cancer and identify therapeutic strategies for targeting the WNT pathway.
  • The team will investigate which WNT pathway signaling proteins are expressed in advanced prostate cancer patient samples and whether tumor cells or other cell types in the tumor microenvironment express these proteins.
  • The role of WNT signaling in tumor vs. non-tumor (stromal) cells within prostate tumors will be investigated in preclinical models. Whether stromal WNT signaling affects prostate cancer progression, and whether the TGFβ signaling pathway is involved in these effects will be determined. This knowledge will instruct whether simultaneous inhibition of the WNT pathway in both tumor and stroma is beneficial or should be avoided.
  • The WNT signaling pathway includes 19 WNT ligands and 10 different FZD receptors. The team will investigate whether targeting multiple FZD receptors has therapeutic potential for the treatment of prostate cancer in preclinical models.
  • If successful, this project will detail the role of the WNT pathway in prostate cancer and identify optimal therapeutic strategies for targeting WNT.

What this means to patients: The WNT signaling pathway is a common cancer driver and may be a promising therapeutic target in prostate cancer. Dr. Xin and team will identify which WNT proteins are expressed by which cells in prostate tumors, and determine their role in prostate cancer biology and as potential therapeutic targets. The knowledge gained from this project will advance the development of successful WNT-targeting therapeutics in prostate cancer.