Stronger together: A successful combination to treat advanced prostate cancer

Akash Patnaik, MD, PhD, in UChicago laboratory

Akash Patnaik, MD, PhD, is an accomplished physician-scientist and national expert in prostate cancer research at the UChicago Medicine Comprehensive Cancer Center.

Most cases of prostate cancer are not fatal; however, prostate cancer that has spread and is not responding to standard hormonal treatments, known as metastatic castration-resistant prostate cancer (mCRPC), carries a poor prognosis.

Currently, researchers are looking for new ways to address this longstanding treatment challenge by testing novel therapeutic options, including cancer therapies that identify and attack specific types of cancer cells. One such drug is cabozantinib, a drug that blocks certain proteins that drive the rapid increase and survival of cancer cells, thus inhibiting the growth of the tumor. It may also prevent angiogenesis, the growth of new blood vessels that tumors need to grow.

This new drug was tested on advanced prostate cancer through a large, phase III clinical trial, named COMET-1. The trial was halted in 2014 when early results showed the drug did not extend survival in a heavily pre-treated mCRPC patient population.

Renewed Hope

The results of that study were puzzling to Akash Patnaik, MD, PhD, an accomplished physician-scientist and national expert in prostate cancer research at the UChicago Medicine Comprehensive Cancer Center. The Comprehensive Cancer Center is a major center for conducting prostate cancer research through the National Cancer Institute and private sponsors.

Patnaik focuses on translating novel therapies from the laboratory to early-stage clinical trials. He was curious about why cabozantinib showed promising activity in a phase II trial of patients with mCRPC, but did not extend survival in a larger phase III trial. He reasoned that a better understanding of the drug’s mechanism of action and its impact on the unique immune environment within the tumor would help identify patients who may respond to it.

At that point, Patnaik’s laboratory began studying cabozantinib’s effects in a laboratory model of advanced prostate cancer. Patnaik’s team observed that cabozantinib- stimulated tumor cells released immune cell trafficking molecules called chemokines. These proteins send out a signal to attract neutrophils, a type of white blood cell that helps heal damaged tissues and resolve infections. This resulted in neutrophils swarming into the tumor and clearing out cancer cells.

The study results were published in