With a new $2 million federal grant, a researcher at 杏吧视频 School of Medicine will lead a team to further explore preliminary findings of an effective treatment for colorectal and possibly other cancers.
The grant, from the National Institutes of Health鈥檚 National Cancer Institute, supports the team鈥檚 promising results recently published in .
鈥淲e reported a novel discovery that some cancer medications trigger 鈥榗ell blasters鈥 to kill cancer,鈥 said Zhenghe 鈥淛ohn鈥 Wang, the Dale Cowan鈥揜uth Goodman Blum Professor of Cancer Research and chair of the Department of Genetics and Genome Sciences at the School of Medicine.
Wang is also co-leader of the Cancer Genomics and Epigenomics Program at the Case Comprehensive Cancer Center (Case CCC).
Case CCC members David Bajor, an assistant professor at the School of Medicine and an oncologist at University Hospitals, and Alok Khorana, a professor at the School of Medicine and the Sondra and Stephen Hardis Chair in Oncology Research at Cleveland Clinic, are Wang鈥檚 collaborators on a clinical trial to test a new cancer treatment.
Their findings
White blood cells are the immune system鈥檚 first line of defense against bacterial infection. Neutrophils, the most abundant white blood cells, can undergo a self-destructive process to release web-like structures鈥攃alled 鈥渘eutrophil extracellular traps,鈥 or NETs鈥攖o trap and kill bacteria, Wang explained.
In their study, the researchers found that combining two chemotherapy drugs (CB-839 and 5-FU) stopped the growth of a type of colon cancer in mouse models that involves PIK3CA鈥攁 gene that controls cell growth. They credited the success partly on NETs, because the drugs weren鈥檛 as effective when the traps were disturbed.
鈥淲e found that patients with tumors that have increased amounts of NETs after the drug treatment survived longer,鈥 Wang said. 鈥淲e found that certain cancer drugs hijack these neutrophils to kill cancers using extracellular traps. So, our study reveals a new way cancer drugs work, paving the way for the design of new cancer treatments.鈥
The study could have a broader impact beyond colorectal cancer, Wang said, because PIK3CA is mutated in about 20% of all human cancers. The mechanisms identified in the study also may apply to other NET-related diseases, he said.
The next steps, he said, are to understand how chemotherapies modulate NET production and then use what they learn to design novel cancer treatments.
For more information, contact Bill Lubinger at william.lubinger@case.edu.
This article was originally published Feb. 8, 2024.
