Newswire (Published: Tuesday, December 17, 2019, Received: Tuesday, December 17, 2019, 6:06:23 PM CST)
Word Count: 503
2019 DEC 17 (NewsRx) -- By a
Resistance occurs because a small percentage of prostate cancer cells are completely impervious to the therapies, and actually thrive when the drugs are used. Targeting this subset of virulent cancer cells is the focus of a study led by
The researchers, publishing online
“We noticed in prostate cancer there are two types of cells,” said senior author Jiaoti Huang, M.D., Ph.D., chair of Duke’s
“Our hypothesis was that this minor population, because they have the ability to survive, contribute to tumor recurrence,” Huang said. “And that’s exactly what we found.”
Huang and colleagues isolated the neuroendocrine cells from fresh human prostate cancer tissue and studied them in the lab. In early-stage prostate cancer, they constitute no more than 1% of all tumor cells, but their numbers are much larger in late-stage and metastatic disease, and they make up almost all of a particularly lethal form of prostate cancer called small cell neuroendocrine carcinoma.
Current prostate cancer treatments exclusively target the majority population of luminal tumor cells, and they do that job well. But not only do hormone therapies leave neuroendocrine tumor cells untouched, the researchers found, they actually enrich the neuroendocrine cell population.
This occurs because tumor growth is driven by a receptor on the surface of neuroendocrine cells called CXCR2, which creates the optimal environment for prostate tumor cells to proliferate and spread. CXCR2 is also expressed by immune cells and involved in inflammation, and a drug that inhibits its function is being developed for patients with chronic obstructive pulmonary disease (COPD).
Huang’s research team tested the drug, navarixin, in laboratory and animal studies, demonstrating that it killed hormone-resistant tumors in combination with enzalutamide, where enzalutamide failed on its own.
“Because CXCR2 is ubiquitously expressed by neuroendocrine cells in prostate cancer of all stages, targeting CXCR2 may particularly benefit patients whose tumors are advanced, recurrent, and resistant to currently available therapies,” Huang said.
“The real implications of our findings need to be tested in clinical settings to determine whether patients with advanced prostate cancer benefit from CXCR2 inhibition, alone or in combination with a hormone inhibitor,” he said.
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