Prostate cancer is the most-commonly diagnosed malignancy and the second leading reason for cancer death amongst men in america. In its ever-indelicate world, the stubborn disease can proceed to grow even when the quantity of testosterone within the body is reduced to very low levels, thus earning the clumsy name: castrate-resistant prostate cancer (CRPC). It poses a significant clinical challenge as a protein called the androgen receptor (AR) stays behind as a critical player in cancer, changing its behavior in CRPCs.

Androgen-deprivation therapy, which is a treatment that reduces the degrees of male hormones, is the first-line treatment for locally advanced or metastatic prostate cancer. Despite initial responses to the therapy, nearly all patients eventually develop CRPC inside a couple of years. It’s now well recognized that CRPC continues to be depending on AR signaling.

“Understanding the triggers that cause changes in AR’s activity is significant for developing higher treatments for CRPCs,” said Ping Yi, assistant professor of biology and biochemistry, who’s leading a team investigating CRPC. Yi’s research is published in PNAS. Her research team includes Ramesh Singh, Lance Lumahan and Hong Shen, Department of Molecular and Cellular Biology, Baylor College of Medicine; and Steven Nguyen, Department of Biology and Biochemistry, Center for Nuclear Receptors and Cell Signaling, University of Houston.

We found a selected chemical modification that happens on the AR protein in certain conditions where the degrees of male hormones are reduced to castration conditions. This modification involves one other protein called TRAF4, which is regularly overexpressed in advanced prostate cancers. We demonstrated that overexpression of TRAF4 results in the conversion of androgen-sensitive prostate cancer cells into castration-resistant cells, each in lab experiments and in live samples. We also found that the TRAF4 protein level is higher in androgen-insensitive lymph node carcinoma cells of the prostate.”

Ping Yi, assistant professor of biology and biochemistry

The findings also suggest that TRAF4 is related to promoting the spread of cancer to other parts of the body. For this research Yi examined cells of patients with metastatic cancer who had previously undergone androgen-deprivation therapy. The researchers also observed that the TRAF4 protein is higher in cancer cells which are now not attentive to androgens in comparison with cells that also reply to androgens.

The researchers imagine that their findings provide a crucial basis for identifying a gaggle of CRPC patients who might respond well to a treatment potentially targeting the precise molecular changes attributable to the AR modification, providing a possible treatment option for this group of patients.