Scientists from the University of Wisconsin–Madison have identified two subtypes of metastatic prostate cancer that respond differently to treatment, information that could one day guide clinicians in treating patients with the therapies targeted to their disease. Building on earlier studies that discovered clinically relevant subtypes of breast cancer and nonmetastatic prostate cancer, researchers identified genetic signatures that can divide metastatic prostate tumors into two types known as luminal and basal.

The researchers also noted that luminal tumors responded better to testosterone-blocking treatments, whereas basal tumors did not benefit as much from this hormone treatment. Basal tumors also consisted of the particularly aggressive form of metastatic disease known as small cell neuroendocrine prostate cancer. Further clinical trials will be necessary before any new diagnostic-based treatment selection is available.

Shuang Zhao, a professor of oncology at the University of Wisconsin School of Medicine and Public Health who helped direct the research, stated, "The reason why these subtypes are important is they respond to hormone therapy very differently. In localized prostate cancer, we've shown that luminal tumors had a bigger benefit from anti-testosterone therapy. We wanted to know if the same pattern extended to metastatic disease."

Along with colleagues at the University of California, San Francisco, and other institutions, Dr. Zhao published his findings on September 23, 2021 in JAMA Oncology.

About 20 years ago, scientists discovered luminal and basal subtypes of breast cancer and discovered that each responds better to different therapies, and this discovery has given physicians greater precision in treating their breast cancer patients. Since breast cancers and prostate cancers share many parallels, including their sensitivity to hormone treatment, in 2016 Dr. Zhao's team aimed to explore whether these parallels extended to different prostate cancer subtypes. They published the first report that identified the luminal and basal subtypes in localized prostate cancer, in which the disease remains confined to the prostate.

The new study expanded the analysis to metastatic cancer and noted that metastatic prostate cancer is much more lethal than its local version, and it is also more challenging to study because small tumors can be in many different parts of the body and are harder to biopsy. To find enough samples to run their analysis, Dr. Zhao's team used multiple large, national studies of metastatic prostate cancer patients.

Dr. Zhao stated, "We pooled all of the data together and assembled the largest metastatic prostate cancer cohort to date." The team ended up with a total of 634 patient samples. The scientists used computational methods to compare the patterns of gene expression in the tumor biopsies. A group of 50 genes determines the basal or luminal nature of breast and prostate cancer, and depending on how active each of these genes is, scientists can separate out the two subtypes.

"Now that we've discovered this pattern, how do we turn this into a test that metastatic patients can benefit from?" said Dr. Zhao, who is also the co-director of the Circulating Biomarker Core at the UW-Madison Carbone Cancer Center.

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