A PCF-funded study published in the prestigious journal Science has identified a new subtype of castration-resistant prostate cancer (CRPC). Understanding how genes and proteins “drive” this particular type of cancer may lead to new treatments.
In the early stages, prostate cancer cells are driven by androgens (e.g., testosterone), which naturally circulate in the body. Androgens are detected by androgen receptor proteins, which send signals to the cells to grow and spread. Androgen-blocking medicines (hormone therapy) are commonly used to treat aggressive or advanced prostate cancer. The cancer initially responds to the treatment that deprives it of its “fuel.” However, eventually the cells adapt and find other ways to grow despite low testosterone, and the cancer becomes “castration-resistant.” New therapies are urgently needed for patients with advanced CRPC.
The two well-studied subtypes of CRPC are called androgen receptor-dependent and neuroendocrine. Now, researchers at Memorial Sloan Kettering Cancer Center and Weill Cornell Medicine, including PCF-funded researchers Dr. Wassim Abida and Dr. Himisha Beltran (Dana Farber Cancer Institute), have identified two more subtypes. Using laboratory and mouse models to mimic the disease, they performed experiments and were able to determine distinct patterns of genes that are switched on or off. These patterns revealed the existence of a “stem cell-like” subtype and “Wnt-dependent” subtype.
The team then cross-checked these patterns against 366 existing patient tumor samples and found that the “stem cell-like” subtype was, in fact, very common – about 25% of cases, second only to the androgen receptor-dependent type. It was also potentially more aggressive, with a shorter time to develop resistance to treatment with the newer types of hormone therapy.
Further analysis identified specific proteins and how they work together to drive this new subtype. These proteins may be “actionable targets,” i.e., targets for development of new medicines that block their activity. The hope is that someday, we will be able to identify patients with “stem cell-like CRPC” and offer them a treatment that is more likely to be effective, based on their tumor’s unique biology.