Hyaluronic Acid May Not Be Good For Cancer
It has be found that usually cancer drugs fail because they cannot penetrate the high-pressure environment of solid tumors. Biophysical Journal published a study that reveals large, naturally occurring molecule called hyaluronic acid is primarily responsible for generating elevated gel-fluid pressures in tumors. Treatment with an enzyme that breaks down hyaluronic acid normalized fluid pressure in tumors and allows vessels to re-expand, overcomes a major barrier to drug delivery in a mouse model of pancreatic cancer.
The gel-fluid phase generates a primary mechanism of drug resistance in pancreas cancer, according to the senior study author Sunil Hingorani of the Fred Hutchinson Cancer Research Center. This also means it may be worth revisiting some of the many agents that have previously failed in pancreas cancer patients and make sure they are first getting into tumor. Also, elevated pressures due to the gel-fluid phase might be present in many other solid types of tumors, so it might be worth seeing to what extent drug delivery can be improved in those settings, too.
The elevated fluid pressure in tumors was first described more than 60 years ago. A number of studies have measured fluid pressures in a variety of tumor models using classical methods as the wick-in-needle technique. Needles containing nylon threads are filled with a solution and connected to a pressure-measuring device. In the past these techniques measured only modestly elevated fluid pressure, which could not account for widespread vascular collapse, which is a major barrier to drug delivery.
These methods only measure freely flowing fluid and overlook the fluid that is trapped in immobile phases. Hingorani and his team suspected a large immobile-fluid phase generated by hyaluronic acid could be a principal driver of high pressures in many solid tumors. They tested this idea with an instrument called a piezoelectric pressure catheter transducer to capture both free and immobile fluid pressures in tumors.
The measurements of fluid pressure using the piezoelectric pressure catheter transducer were much higher than those by the wick-in needle technique. The findings show the hyaluronic acid-dependent immobile fluid phase plays a previously underappreciated role in driving high pressures in solid tumors.
A mouse model of pancreatic cancer with a modified form of an enzyme called hyaluronidase was used. It eliminated the immobile fluid phase and allowed vessels that had collapsed under pressure to re-expand.
A number of randomized clinical trials are examining the safety and effectiveness of hyaluronidase combination therapy in cancer patients. The National Institutes of Health National Cancer Institute, the Lustgarten Foundation and the Giles W. and Elise G. Mead Foundation supported this study. Several authors were employees, consultants and/or shareholders of Halozyme Therapeutics.
–Dr Fredda Branyon
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