News release

From: Peter MacCallum Cancer Centre

New drug targets offer potential pathway for pancreatic cancer treatment

Peter Mac researchers have identified new potential drug targets for pancreatic cancer by uncovering proteins cancer cells rely on to grow and survive.

Pancreatic cancer remains one of the most challenging cancers to treat with the overall five-year relative survival rate approximately 13-14 per cent. Survival depends heavily on how early the cancer is found and whether it has spread to other parts of the body.

The research, led by co-senior author Dr Jennifer Devlin and published in Molecular Cancer Therapeutics, focused on a family of proteins known as transcriptional cyclin-dependent kinases, or tCDKs.

“Cancer cells depend on certain genes being constantly active to support their growth and survival,” Dr Devlin said.

“We wanted to understand whether disrupting the machinery that allows pancreatic cancer cells to keep these genes switched on could expose a weakness that could potentially be targeted with new treatments.”

The researchers tested a range of drugs designed to block different tCDKs in pancreatic ductal adenocarcinoma cells, the most common form of pancreatic cancer.

They found that targeting several of these proteins stopped the cancer cells from growing and multiplying. In particular, pancreatic cancer cells were highly sensitive to drugs targeting four proteins known as CDK9, CDK11, CDK12 and CDK13.

“These proteins help control crucial stages of the process that allows genetic instructions to be copied into RNA, which cells then use to carry out their functions,” Dr Devlin said.

“When we blocked these stages, we saw a strong impact on the ability of pancreatic cancer cells to produce new RNA and to continue multiplying.

“This gives us a clearer picture of which parts of this gene-control machinery pancreatic cancer cells are particularly dependent on, and where there may be opportunities for future treatments.”

“Our findings point to CDK9, CDK11, CDK12 and CDK13 as particularly interesting vulnerabilities in pancreatic cancer cells and provide a foundation for further research into how these targets might ultimately be used therapeutically.”

This study was completed within the Johnstone lab at Peter Mac alongside co-first authors Yvonne Daniel and Ben Martin, co- author Dr Nenad Bartonicek, and co-senior authors Professor Ricky Johnstone and Dr Devlin.