RIP1 kinase as a therapeutic target for pancreatic cancer

Researchers at the NYU School of Medicine have discovered that an experimental drug could be effective against a deadly form of pancreatic cancer when it was used in combination with immune-enhancing therapies.

Using mouse models and human cells grown in the lab, the researchers showed how the experimental drug GSK547 helps checkpoint inhibitors in a more aggressive attack of tumor cells.

The team explained how the immune system attacks foreign 'intruders', such as bacteria, and leaves the cells of the body intact. In laboratory experiments, combination therapy doubled survival at 50 days in mice with pancreatic ductal adenocarcinoma. Mice affected in the same way that only control point inhibitors were administered did not live for more than 25 days.

The team collaborated with the Perlmutter Cancer Center at the NYU School of Medicine and researchers at GlasoSmithKline.

"Our results confirm the potential efficacy of blocking a signaling pathway in pancreatic ductal adenocarcinoma so as to powerfully complement existing treatments," said Dr. George Miller, professor HL Pachter of the NYU Langone Health and Perlmutter, vice president of research within the department. of surgery at NYU Langone.

"If clinical trials succeed, this could be very promising for many people with a terminal illness."

Professor Miller stated that the experimental drug was blocking the action of serine / threonine-protein kinase 1 interacting with the RIP1 receptor. This enzyme regulates the macrophages that attack the tumors, but it modifies the immune system because of the signals of the cancer cells.

In vitro Experiments on human pancreatic cancer cells with the experimental drug showed that twice as many killer T cells were activated and that macrophage-influenced T cell levels that suppressed the immune system were five times less.

"Our approach is designed to turn" cold "tumors that escape the immune system into" hot "tumors, which the system can target," said co-lead author of the study, Dr. Wei Wang, a fellow Postdoctoral Fellow, NYU Langone Department of Surgery. and Perlmutter. "Ultimately, we hope that our future research will reveal that the inhibition of RIP1 kinase can be applied to several cancers that resist control point inhibition."

The study was reported in the newspaper Cancer cell.