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Researchers identify new subtypes of metastatic prostate cancer

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Sept. 23 (UPI) — Researchers have identified two new subtypes of metastatic prostate cancer that respond differently to treatment, they reported in a study published Thursday by JAMA Oncology.

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The information could be used by oncologists to develop targeted therapies best suited to treat the cancer in individual patients, the researchers said.

The two new types of metastatic prostate cancers, or those that have spread to other organs, are called luminal and basal, according to the researchers.

Based on their initial experiments, luminal tumors respond better to testosterone-blocking treatments while basal tumors, which include the particularly aggressive small-cell neuroendocrine prostate cancer, did not benefit as much from hormone treatment, they said.

“The reason why these subtypes are important is they respond to hormone therapy very differently,” study co-author Dr. Shuang Zhao said in a press release.

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“Now that we’ve discovered this pattern, how do we turn this into a test that metastatic patients can benefit from?” said Zhao, a professor of oncology in the University of Wisconsin School of Medicine and Public Health in Madison.

About 20 years ago, scientists discovered luminal and basal subtypes of breast cancer and found that each responds better to different therapies.

Because breast cancers and prostate cancers are similar in that they both respond to hormone treatment, or drugs that block the production of hormones such as testosterone and estrogen, researchers wondered whether they shared these subtypes.

In 2017, Zhao and his colleagues found that localized prostate cancers, or tumors confined to the prostate gland, have the same genetic make-up as luminal and basal breast cancers, with 50 genes determining the subtype.

For this new study, the team expanded the analysis to metastatic prostate cancer, in which the disease spreads from the gland to other organs, using tumor biopsy samples from 634 patients.

They compared the patterns of gene expression in the tumor biopsies and identified luminal and basal types for metastatic cancer.

Once the existence of the subtypes had been confirmed, the researchers then sought to determine how they affected patient survival and response to treatment.

Because the doctors treating patients included in the study did not know about the subtypes at the time, they had to treat the disease without this information, the researchers said.

The resulting variation in treatment produced a natural experiment that Zhao and his team could analyze.

“And we found that just like in localized prostate cancer, the hormone therapies seemed to work better in the luminal tumors than in the basal tumors,” Zhao said.

In addition to the subtypes, the tumors fell onto a spectrum depending on their degree of “luminal-ness” or “basal-ness,” he and his colleagues said.

At one end of the spectrum, there were the hormone-treatment-resistant small cell neuroendocrine prostate cancers, which were the most basal, the researchers said.

At the other end, there were less aggressive luminal subtypes, which responded to hormone therapy.

It is unclear how tumors that lie in the middle of these two extremes respond to different treatments, they said.

Given that metastatic prostate tumors are difficult to biopsy, a procedure in which samples are collected for analysis to determine treatment, the researchers are hoping to develop blood tests that could more easily determine whether they are luminal or basal.

This test would make clinical trials testing the effectiveness of subtyping metastatic tumors much easier, they said.

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