Study identifies potential treatment target for prostate cancer resistant to hormone therapy

Newswise — Prostate cancer is the frequently detected cancerous condition and the second primary factor behind male cancer fatalities in the United States. In its persistent realm, this unwavering ailment can thrive despite significant reduction in testosterone, resulting in the unrefined label: castrate-resistant prostate cancer (CRPC). This presents a substantial medical hurdle since a vital agent known as the androgen receptor (AR) retains its pivotal role, manifesting altered characteristics within CRPC cases.

The primary approach for managing prostate cancer that has spread locally or metastasized is androgen-deprivation therapy (ADT), a treatment aimed at diminishing male hormone levels. Although patients initially respond to this therapy, almost all individuals eventually progress to develop CRPC within a few years. It is widely acknowledged that AR signaling remains a crucial factor in the sustained existence of CRPC.

"Elucidating the factors that induce modifications in AR's functionality holds significance in the advancement of more effective therapies for CRPC," remarked Ping Yi, an assistant professor of biology and biochemistry, who spearheads a research team dedicated to studying CRPC. Yi's findings have been published in the esteemed journal PNAS. The research team comprises Ramesh Singh, Lance Lumahan, and Hong Shen from the Department of Molecular and Cellular Biology at Baylor College of Medicine, as well as Steven Nguyen from the Department of Biology and Biochemistry and the Center for Nuclear Receptors and Cell Signaling at the University of Houston.

"Within certain circumstances where male hormone levels are reduced to castration conditions, we have identified a specific chemical alteration that takes place on the AR protein," explained Yi. "This modification is linked to the presence of another protein known as TRAF4, which is frequently overexpressed in advanced prostate cancers. Through laboratory experiments and analysis of live samples, we successfully demonstrated that the overexpression of TRAF4 prompts the conversion of androgen-sensitive prostate cancer cells into castration-resistant cells."

Yi further added, "Additionally, our investigation revealed that the level of TRAF4 protein is elevated in androgen-insensitive lymph node carcinoma cells of the prostate."

The research findings indicate a potential correlation between TRAF4 and the facilitation of cancer metastasis to distant sites in the body. To investigate this, Yi analyzed cells from patients with metastatic cancer who had previously undergone androgen-deprivation therapy. Notably, the research team observed that the levels of TRAF4 protein were elevated in cancer cells that were unresponsive to androgens, as opposed to cells that still demonstrated responsiveness to androgens. These observations provide valuable insights into the role of TRAF4 in the progression of prostate cancer and its association with treatment resistance.

Based on their discoveries, the researchers are confident that their findings establish a crucial foundation for identifying a subset of CRPC patients who may exhibit favorable responses to a treatment strategy focused on targeting the specific molecular alterations triggered by the AR modification. This promising avenue potentially offers a treatment option for this particular group of patients, opening up possibilities for improved therapeutic interventions tailored to their specific needs.