Cells help treat resistance in prostate cancer: Study

Prostate cancer is the most diagnosed form of cancer and the second-leading cause of cancer-related deaths in males in the US. This is largely due to incomplete knowledge of the cellular drivers behind the disease’s progression and the risk of progressing to castration-resistant prostate cancer (CRPC).
Scientists have described prostate cancer cell dynamics at a single-cell resolution throughout the course of the disease, from the first stages to the point of androgen independence, where the tumour no longer responds to hormone restriction therapy. Published in eLife, the study in mice reveals an expansion of intermediate cells in prostate cancer, which correlates with resistance to treatment and poor clinical outcomes in humans.
These cells are castration-resistant, meaning they continue to grow without testosterone and could explain how prostate tumours become resistant to hormone-related treatments. The prostate gland epithelium, a type of body tissue that forms the surface of glands and organs, is typically composed of two types of epithelial cells, basal cells and highly-differentiated luminal cells. However, a more stem-like, castration-resistant intermediate of the luminal cells has previously been proposed.
Alexandre Germanos, a Ph.D. candidate in Molecular and Cellular Biology at the University of Washington, US, and a graduate student at the Division of Human Biology, Fred Hutchinson Cancer Center, US, said, “It has been suggested that normal luminal cells are able to transition onto these progenitor cells under castrate conditions. There is evidence that these cells contribute to the initial development of tumours in the prostate and resistance to treatment in advanced cancers, although this is yet to be confirmed in other models of CRPC.”
Germanos and his colleagues used a mouse model of CRPC to create an “atlas of prostate cellular composition and evolution” throughout the disease. Their findings suggest that a 5-gene signature derived from mouse prostate cancer models may be important in understanding human disease. The presence of this gene signature may serve as a useful prognostic tool for predicting treatment resistance and outcomes in patients. The authors call for further studies to validate this signature's role and intermediate-like cell populations in individuals with prostate cancer.