A unique way to ‘prime’ the tumor microenvironment could help chemo work better for pancreatic cancer patients, one of the highly deadly types of colon cancer.
The findings have prepared the path for a drug study to determine if the therapeutic technique is successful for individuals with pancreas ductal carcinoma.
Prescribing Chemotherapy For Pancreatic Cancer May Help
“We expect to increase survival rates for pancreatic cancer patients by making cancer cells more responsive to treatment,” says Professor Paul Timpson, Cancer Research Theme Leader at the Garvan Institute and co-senior author of the research published in Science Advances. “This work is an excellent example of cutting-edge laboratory research leading to industry collaboration and future clinical translation.”
By lowering the flexibility and thickness of the connective called the stromal in pre-clinical studies, a group was able to improve the tumors’ responsiveness to chemo and minimize tumor spreading by up to 50%.
“We wanted to try and improve on chemotherapy using a unique approach—targeting the environment around the tumor to make cancer more sensitive to treatment,” says Dr. Kendelle Murphy, first author of the paper.
The scientists look into FAK, a protein generated by pancreatic that promotes cancerous cells proliferate, mobilize, and spread by increasing the rigidity of the stromal. The scientists studied if inhibiting FAK with an investigational drug could ‘main’ cancerous cells to be more easily eliminated by chemo by employing state-of-the-art live cell imaging tools to demonstrate how living pancreas tumors in mice model require treatments.
“When we administered a treatment that targeted FAK before chemotherapy in our experimental models, that’s when we saw the most benefits,” says Dr. Murphy.
For those who suffer from different types of cancer, the experts suggest chemotherapy as it is proven the safest option to remove the virus from the body. The same option proves useful for pancreatic cancer if it is followed under the guidance of an expert.
Pancreatic carcinoma is a type of colon cancer that is invasive as one of the worst fatal diseases. With advancements in combo therapy, the 5-year mortality probability is fewer than those in 10, and much less than 3 percent if the disease already has spread.
“Merlin is a protein that is produced at different levels in pancreatic cancer patients. We found that low levels of merlin in our experimental pancreatic cancer models resulted in our ‘priming’ combination approach targeting FAK being more effective,” says Dr. David Herrmann, co-senior author of the study.
The scientists also observed that the amounts of merlin, a specific protein in carcinoma cells, could aid in determining which patients might gain more from FAK inhibition.
“We hope that by determining which tumors produce less merlin, we will be able to identify which patients are likely to benefit most from our new combination approach.”
“It is exciting for Amplia to be able to work with Garvan’s extensive experience in FAK biology, cancer biology, and clinical expertise. The results of the pre-clinical studies have provided important insights and validated our decision to progress our FAK inhibitor, AMP945, to Phase II clinical trial in pancreatic cancer patients,” says Amplia CEO and Managing Director, Dr. John Lambert.
The results will be studied as half of a future medical study conducted in partnership with Melbourne-based Amplia Pharmaceuticals Ltd, which plans to start Phase Ii studies of its FAK antagonist AMP945 next summer to see if the treatment is successful in individuals.
“The survival rates of pancreatic ductal adenocarcinoma patients are dismal and have been largely unchanged for decades,” adds Professor Timpson. “Our approach is a promising new clinically relevant avenue to improve on current treatments, and potentially make a real difference for patients.”
