New drug combination shows promise in small cell lung cancer

Researchers at the Icahn School of Medicine at Mount Sinai have made a promising breakthrough in the treatment of small cell lung cancer (SCLC). Their study, published in Scientific advances and entitled “ATR Inhibition Activates Cancer Cell cGAS/STING-Interferon Signaling and Promotes Anti-Tumor Immunity in Small Cell Lung Cancer” presents an exciting new approach that offers hope to patients with this challenging disease.

Small cell lung cancer is one of the most aggressive types of cancer. It accounts for about 10 to 15% of all lung cancer cases in the United States, with about 30,000 to 35,000 new cases occurring each year. Unfortunately, by the time most patients are diagnosed, the cancer has already spread, making treatment difficult. Current treatments such as chemotherapy and immunotherapy provide only temporary relief and the five-year survival rate is less than 10%.

“We focused on ATR (ataxia telangiectasia and Rad3-related protein), which plays a key role in repairing DNA in cancer cells. By inhibiting ATR, we make these cancer cells more susceptible to treatments and improve the immune system's ability to attack,” said Triparna Sen, Ph.D., associate professor of oncological sciences and director of the PDX Lung Cancer Platform at Icahn Mount Sinai.

New treatment strategy: double whammy

The study examined the effects of a new drug called berzosertib (M6620/VX970) in combination with another drug, topotecan, to treat SCLC patients with relapse.

“Our results suggest that this combination could be very effective, especially for patients whose cancer has returned,” noted Dr. Sen. Research also suggests that using ATR inhibitors along with anti-PD-L1 antibodies, a type of targeted immunotherapy called an immune checkpoint inhibitor that helps the immune system recognize and attack cancer cells, may improve results could improve further.

The study showed that inhibiting ATR activates a part of the immune system known as the cGAS-STING pathway. This leads to an increase in immune signals such as interferons and chemokines, which help the immune system recognize and attack cancer cells more effectively.

“We have previously found that DNA damage response proteins are effective targets for small cell lung cancer, and this research, conducted jointly by postdoctoral researchers Hirokazu Taniguchi, MD, Ph.D. and Subhamoy Chakraborty, Ph.D. “By targeting ATR and improving the immune response, we are opening up new avenues for better treatment options,” explained Dr. Sen.

The Mount Sinai team plans to propose a clinical trial to test these new treatments by 2025. They hope this research will benefit other difficult-to-treat cancers.