Scientists identify multiple cell types that may contribute to treatment resistance in prostate cancer

Researchers have characterised prostate cancer cell dynamics at a single-cell resolution across the timespan of the disease — from its beginning to the point of androgen independence, where the tumour no longer responds to hormone deprivation therapy.

Their study in mice, published today in eLife, reveals an expansion of intermediate cells that occurs 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 in the absence of testosterone and could explain how prostate tumours become resistant to hormone-related treatments.

Prostate cancer is the most diagnosed form of cancer, and the second-leading cause of cancer-related deaths in males from the US. This is in large part due to an incomplete knowledge of the cellular drivers behind the disease’s progression and the risk of progressing to castration resistant prostate cancer (CRPC).

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 (cells which have altered in form). However, a more stem-like, castration-resistant intermediate of the luminal cells has previously been proposed.

“It has been suggested that normal luminal cells are able to transition into these progenitor cells under castrate conditions,” says lead author Alexandre Germanos, a PhD 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. “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.”

To study this further, Germanos and colleagues used a mouse model of CRPC to create an ‘atlas of prostate cellular composition and evolution’ through the course of the disease.

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