Cross talk between cancer cells and the stroma may be the key to turning around the appalling mortality rate associated with pancreatic cancer.
Professor Minoti Apte, director of the Pancreatic Research Group at the Ingham Institute, told Australian Gastroenterology Week a multipronged approach to pancreatic cancer was required.
“It is increasingly acknowledged that the stroma is important in cancer biology and that it cannot really be ignored if you want to improve outcomes, particularly in pancreatic cancer.”
She said there was clear evidence that activated pancreatic stellate cells played a role in pancreatic fibrosis and the progression of pancreatic cancer.
“Our group was looking at the stroma because we were interested in the fibrosis of chronic pancreatitis. When we found stellate cells were doing much more than sitting there making collagen, we starting looking at cross talk.”
Professor Apte said stellate cells helped create a microenvironment that supported the primary tumour as well as cancer metastasis.
Stellate cells remodeled the extracellular matrix, stimulated angiogenesis, interacted with immune cells and promoted neurite outgrowth.
“The extent of stroma can be different in different patients and I think the stroma will be important where there are highly active stellate cells. Those patients will need a stroma-targeting therapy,” she said.
“In other patients with very dense collagen deposition but no active cells, physically getting rid of the stroma may be needed to get better access for anti-cancer drugs.”
Professor Apte said a number of novel therapies were under investigation including vitamin D receptor ligands, heat shock protein 70 inhibitors and inhibitors of the hepatocyte growth factor (HGF)-c-MET pathway.
“We think the HGF-c-MET pathway is active not only in the way the stellate cells talk to cancer cells but also the way stellate cells talk to blood vessel cells. So we are hitting two different targets in the stroma, not just one.”
However she said clinical trial results had been ‘variable and modest’ so far.
“Combination therapy with gemcitabine only improves survival by about 1.8 months in the clinic; maybe up to three months. But maybe we are not using the right therapies so far, or the dose has to be titrated, or cross talk between stromal and cancer cells needs to be targeted earlier.”
Professor Apte said she was also very interested in the fact that pancreatic stellate cells were circulating in the blood along with tumour cells.
“Because pancreatic cancer metastasises so early there must be something very efficient about the cells that are being sent out from primary tumour. We think that the stellate cells that are travelling with the cancer cells are probably helping them. That is a very novel thing.”