Scientists show how to attack the “fortress” that surrounds pancreatic cancer tumors-ScienceDaily

“Pancreatic cancer has had minimal improvement in survival over the last 40 years. Without immediate action, it is predicted to be the second largest cancer murderer in the world by 2025,” UNSW said. Associate Professor Phoebe Phillips, Senior Author of Medicine & Health, said.

“But our latest advances mean that I am the most optimistic and hopeful of my career today.”

Pancreatic cancer is notorious for being difficult to treat due to the dense scar tissue surrounding the tumor. The tissue acts like a fortress that prevents the delivery of chemotherapy.

“This scar tissue is produced by important” helper cells, “also called cancer-related fibroblasts, which are mobilized to support their growth and spread. However, these helper cells are ignored in current therapeutic strategies, “A / Prof said. Philips says.

“Our approach affects both tumor and helper cells, making it ideal for overcoming disease aggression and drug resistance.”

In today’s treatise, the team presents a new way to metabolically rewire helper cells by targeting a specific protein called SLC7A11. This blocks the tumor-promoting activity of the cells and reduces the scar tissue produced.

“We found that turning off SLC7A11 in mice with pancreatic tumors killed pancreatic cancer cells directly, spread the tumor cells throughout the body, and reduced scar tissue fortress,” said A / Prof postdoctoral fellow. One Dr. George Sharbeen said. The Philips laboratory that led the work.

Comprehensive model, detailed investigation

SLC7A11 has previously been studied in pancreatic cancer cells, but this is the first study to show that it also plays an important role in non-tumor helper cells.

“In other words, we have identified new” double-cell “therapeutic targets that address both tumor cells and their helpers, overcoming the current limitations of standard chemotherapy. The team used several complementary models, including patient-derived pancreatic cancer cell lines and helper cells, a 3D bench model including an explant model that maintains fragments of human pancreatic tumor tissue, and multiple mice. A model of pancreatic cancer that improved the clinical translatability of findings.

“We also provided gene therapy that inhibits SLC7A11 using state-of-the-art nanomedicine developed in an interdisciplinary collaboration with engineers (Professor Cyril Boyer of UNSW and Professor Thomas Davis of the University of Queensland). The drug is small and can penetrate the scar tissue of pancreatic cancer, “said co-lead author Joshua McCarroll, associate professor at the Institute for Pediatric Cancer.

Clinical trials are about to begin

The team’s findings laid the foundation for A / Prof-led clinical trials. Professor David Goldstein, a collaborator with Philips and UNSW Medicine, was funded by the recently awarded Cancer Institute NSW Translational Program Grant.

“This study reuses an anti-arthritis drug called sulfasalazine for the treatment of patients with pancreatic cancer who have tumors with high levels of SLC7A11. It has been shown to strongly inhibit SLC7A11 in patients. More than half. It may improve treatment response and ultimately improve survival in these patients, “A / Prof said. Philips says.

Researchers say the opportunity to reuse existing drugs already in the clinic will help them progress faster.

“By using the approved drug, we were able to bring this work to the clinic much faster than if we started developing the drug from scratch,” says A / Prof. Philips.

“We are doing this exciting development from the laboratory bench to the clinic with the sole purpose of improving the outcome of patients with pancreatic cancer.”

The research team hopes to analyze and publish the first set of results for the trial within three years.

Improving results that haven’t changed for decades

In addition to clinical trials, the team now wants to evaluate how their approach interferes with the exchange of nutrients between tumor cells and helper cells. They also want to identify the ideal drug to combine with their therapeutic approach to enhance antitumor effects.

Pancreatic cancer is a very deadly disease, with only 1 in 10 patients surviving for more than 5 years. In 2020, an estimated 4000 Australians were diagnosed with pancreatic cancer. About 90% of them die, often within a few months of diagnosis.

“Clearly improved treatments are needed to turn these dire statistics around, and we hope that the clinical translation of our findings will ultimately increase the number of pancreatic cancer survivors,” A said. / Prof says. Philips.

“We will not give up until we improve the quality of life of our patients and provide effective treatment.”

This work was funded by NHMRC, Cancer Institute NSW, and PanKind (Australian Pancreatic Cancer Foundation).