Kyoto Researchers Find Key to Treat Resistant Cancer

Colorectal cancer is Japan's most diagnosed cancer and the second leading cause of cancer death, but doctors have been frustrated for years. The widely used immunotherapy drug Opdivo fails to work in 85% of colorectal cancer patients, and for those with advanced, spreading tumors, that number jumps to 95%.

Now researchers at Kyoto University have figured out why. They discovered that cells called fibroblasts surround cancer tumors and create a protective barrier that blocks immune cells from attacking the cancer.

Fibroblasts normally help repair damaged tissue in the body. But when they gather around colorectal cancer cells, they become part of the problem instead of the solution.

The team found that these fibroblasts release a specific protein that stops immune cells from doing their job. Even worse, they physically block CD8+ T cells, the immune system's cancer-fighting soldiers, from reaching the tumor at all.

But here's where the breakthrough gets exciting. The researchers tested their theory on mice with colorectal cancer by stopping the mice from producing that troublesome protein, then giving them immune checkpoint inhibitors like Opdivo.

The results were dramatic. The cancer in the mice almost completely disappeared.

The Ripple Effect

Dr. Yuki Nakanishi, a lecturer at Kyoto University Hospital and team member, sees enormous potential for patients who have run out of options. The team is now developing two new drugs: one that stops fibroblasts from making the protein, and another that blocks the protein's activity.

These new drugs could be combined with existing immunotherapy treatments to create a powerful package therapy. For patients with advanced colorectal tumors that can no longer be removed through surgery, this could offer what Nakanishi calls "a radical cure."

The combination approach could also work earlier in treatment. Doctors might use it to shrink tumors before surgery, making operations safer and more effective.

The research has already been published in the prestigious journal Nature Communications. With colorectal cancer affecting hundreds of thousands of people worldwide each year, this discovery addresses a massive unmet medical need.

The team is working to move these findings from the laboratory to clinical trials as quickly as possible. For the 85% of colorectal cancer patients who watch other treatments fail, this research represents genuine hope where there was little before.

Sometimes the biggest breakthroughs come from asking a simple question: not just how to make existing treatments stronger, but why they fail in the first place.