Hormone Therapy Can Make Prostate Cancer Worse

Prostate cancer can sometimes withstand and outplay a standard hormone therapy, causing cancer to spread, reports a study published in the Journal of Clinical Investigation (JCI). The findings of the researchers at Cedars-Sinai also point to a simple blood test that may help doctors predict when this type of hormone therapy resistance will occur.

The most common type of cancer, adenocarcinoma, is curable in its early stages and generally responds well to therapies, including those that target androgen -- a male sex hormone that stimulates tumor growth. However, cancer becomes resistant to androgen-targeted therapy, in certain patients, and starts to recur or spread. According to the study, one possible reason for that resistance appears to be that the therapy causes some adenocarcinoma cells to become neuroendocrine cancer-type cells -- a rare type that normally appears in fewer than 1 percent of prostate cancer patients.

"This transformation is a problem because neuroendocrine prostate cancer is especially aggressive, metastasizes more readily and is more resistant to both androgen-targeted therapy and chemotherapy," said Neil Bhowmick, the lead author of the study.

“About one-fourth of the patients who receive androgen-targeted therapy may relapse with tumors that show features of neuroendocrine prostate cancer and develop the treatment-resistant disease, according to published research,” he added.

Bhowmick and associates conducted a study to examine how cancer cells interact with the supporting cells near the tumor, referred to as the tumor microenvironment, in laboratory mice. They found these interactions raised the level of the amino acid glutamine, turning the supporting cells into “factories” that supplied fuel for the cancer cells.

The team also examined how androgen-targeted therapy affected the cancer microenvironment.

“To our surprise, we found this type of therapy further changed the cellular environment in a way that caused adenocarcinoma cells in the prostate to transform into neuroendocrine cancer-type cells,” said Bhowmick, professor of Medicine and Biomedical Sciences.

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As the final step in validating the findings in mice, investigators compared levels of glutamine in the plasma of small groups of patients – one with treatment-responsive prostate cancer and the other with treatment-resistant prostate cancer. The researchers found that levels of glutamine were higher in the second group.

“This finding has potential implications for treating prostate cancer patients, said Edwin Posadas, associate professor and clinical chief of the Division of Hematology/Oncology in the Department of Medicine at Cedars-Sinai.

“The study raises the possibility that a simple blood test measuring glutamine might be able to pinpoint when androgen-targeted therapy is failing in a prostate cancer patient and even predict when therapy resistance will occur,” said Posadas, who co-authored the study. He said the team is designing a new study to test this hypothesis.

Prostate cancer is the second-leading cause of cancer death in men, behind lung cancer, killing nearly 30,000 in the U.S. each year, according to the American Cancer Society.

For reference log on to 10.1172/JCI99397