New research describing the fundamental biology behind Amplia Therapeutics’ (ASX: ATX) planned phase 2 clinical trial on pancreatic cancer patients has highlighted the potential benefits of using a focal adhesion kinase (FAK) inhibitor prior to administering standard chemotherapy.
Published by Garvan Institute of Medical Research, the study was led by Professor Paul Timpson who works in FAK biology at Garvan and is a member of Amplia’s scientific advisory board.
Professor Timpson’s team was able to show that mice implanted with human pancreatic cancer tissue could be pre-treated with a FAK inhibitor (or ‘primed’) to increase the responsiveness of a tumour to subsequently administered first line gemcitabine chemotherapy.
The inhibitor could enhance a tumour’s response to chemotherapy by reducing the stiffness and density of connective tissue known as a stroma, and reduce cancer spread by up to 50%.
FAK priming also reduced the metastatic spread of tumour cells to secondary sites such as the liver.
Amplia chief executive officer John Lambert said the new approach of priming the tumour environment may improve how effective chemotherapy is for pancreatic cancer.
“There have been several publications over the last two years that have highlighted the potential of FAK inhibitors in pancreatic cancer, including their ability to work synergistically with chemotherapy agents,” he said.
“This latest study from our collaborators at Garvan is particularly exciting as its replicates the approach that we are taking to treat first-line pancreatic cancer patients in our phase 2 trial.”
Professor Timpson said the research offered a promising approach for improving patient outcomes.
“By pre-treating the tumours with the FAK inhibitors we are changing the stiffness as well as the amount and deposition of stromal tissue surrounding the cancer cells,” he said.
“On this softer surface, the cancer cells became stalled, rendering them more sensitive to chemotherapy [so] effectively, we are increasing the window of vulnerability of these cells to chemotherapy, reducing pancreatic cancer growth and spread in our models.”
He said the work was a “powerful example” of cutting-edge research in the laboratory leading to partnership with industry and potential clinical translation.
Pancreatic cancer diagnosis affects approximately 60,000 people in the US and nearly 4,000 people in Australia each year.
It is believed to be one of the most deadly cancers with a five-year survival rate of between 5% and 10%.
The only potential cure is surgical excision however only 20% of patients are eligible for surgery with the remainder having either localised, non-resectable (unable to be treated with surgery) or metastatic disease.
The standard first-line therapy for these patients is chemotherapy with either gemcitabine or the combination drug Folfirinox which is also used to treat bowel cancer.
Around 50% of first-line pancreatic cancer patients are able to receive a second-line therapy, but there is currently no standard treatment.