Experts honing in on connection between cancer, breakdown of the Y chromosome among men

Cancer experts at Cedars-Sinai are honing in on a better treatment for men battling cancer who also show a loss of the Y chromosome. They say immunotherapy can be particularly effective in these patients.

Champion weightlifter Paul Paolella, 41, was at the height of his competitive career in 2013. But his progress started to falter.

"I knew something was wrong. I had been avoiding going to a doctor for some time. I had blood in my urine consistently." he said.

During an emergency visit at Cedars-Sinai, scans clearly showed he had bladder cancer. But, knowing this gave him focus.

"It was a weight lifted off my shoulders and I knew Ok, now I needed to enter into an honest fight with this thing," Paolella said.

The battle would be hard fought. Doctors removed his bladder and fashioned a new one.

He went back to training, but 18 months later Paul felt more pain. A scan showed the cancer had spread.

"He said we found something in your right lung," he recalled.

Another surgery, this time followed by chemotherapy. A year later, the cancer had spread to his left lung.

"That was, emotionally, the hardest time for me," Paolella said.

Paul was running out of options until the FDA approved a treatment to bolster his immune system.

"The immunotherapy was a cycle breaker for me," he said.

So how and why did immunotherapy work? Dr. Dan Theodorescu and his colleagues at Cedars-Sinai Cancer have a theory, and it has to do with the breakdown and loss of the Y chromosome in about 10-30% of men.

"Men that have this do have higher incidence and higher risk, if you will, for cancer and neurological disease and heart disease," said Theodorescu.

But his team found something else about the cancer in these men. The Y chromosome loss made it more aggressive, but it also made it more vulnerable.

"The cancer becomes more sensitive to things like checkpoint blockade, which is a form of immunotherapy," he said.

At this point, a clinical test to determine Y chromosome status for patients like Paolella does not exist, but Theodorescu said that's the next step.

"We want to put that test in the hands of practitioners so we can do studies to see how well the test predicts the response," he said.

Following immunotherapy, Paolella has been cancer free for five years. He doesn't dwell on why all this happened to him, but prefers to focus on the lessons learned. Beating cancer is a partnership.

"I'm a trainer. I believe in discipline. I believe in hard work. I believe in showing up. And it was my responsibility to make myself healthy and to get strong again," Paolella said.