Researchers discover what causes cancer drugs to fail

The high-pressure environment of pancreatic cancer tumours are behind most drugs failing, according to researchers from the Fred Hutchinson Cancer Research Center

In a study the researchers found that one of the reasons pancreatic cancers are so hard to treat is because they are filled with so much pressure, that blood vessels collapse and cancer-fighting drugs can’t get in.

The study revealed that Hyaluronic acid, a large, naturally occurring molecule, is primarily responsible for generating elevated gel-fluid pressures in tumours. 

Only strategies that melt away the acid inside the tumours will relieve enough pressure to reopen the tumours’ crushed blood vessels and allow chemotherapy in, the study suggests.

“Unless you know the source [of pressure inside pancreatic tumours], you don’t know how to tackle the problem,” said Sunil Hingorani, the study’s senior author.  

A hyaluronidase treatment uses a family of enzymes that degrade hyaluronic acid and according to the study, holds promise for improving patient outcomes for drug-resistant cancers.

The team conducted a hyaluronidase treatment in a mouse model of pancreatic cancer and found that it broke down hyaluronic acid as well as normalised the fluid pressure in tumours, allowing vessels to re-expand and thereby overcome a major barrier to drug delivery, IndiaWest reported.

Hingorani said: “The findings show that the hyaluronic acid-dependent immobile fluid phase plays a previously underappreciated role in driving high pressures in solid tumours.

“Elevated pressures due to a gel-fluid phase may be present in many other solid tumour types, so it may be worth seeing to what extent drug delivery can be improved in those settings as well.”