Attacking Pleural Mesothelioma From the Inside Out

There is new evidence that manipulating the process of protein synthesis inside cancer cells could be the key to improving mesothelioma  outcomes for certain patients.

A new study published in the Journal of the American Medical Association (JAMA) Oncology suggests that using a drug to lower the levels of the amino acid arginine can slow the spread of pleural mesothelioma and extend survival in patients who are deficient in a particular enzyme.

Overcoming Mesothelioma Treatment Resistance

One of the most challenging aspects of malignant mesothelioma is that it is highly resistant to most kinds of cancer treatments. Patients and their doctors are often at a loss as to what to try next when chemotherapy, surgery, and radiation fail.

Although not every mesothelioma patient is a fit for this new kind of therapy, for those who are, the study suggests that it could help conventional cancer treatments work better.

ASS1-Deficiency and Mesothelioma

The research detailed in JAMA Oncology hinges on arginine, an amino acid necessary for cells – including mesothelioma cells – to make the proteins that allow them to live and replicate.

But a multi-center phase 2 randomized clinical trial demonstrated that 68 of 201 mesothelioma tumors were deficient in argininosuccinate synthase (ASS1), an enzyme necessary for arginine synthesis.

In these ASS1-deficient people, using a drug to artificially reduce the amount of arginine in the body made their malignant mesothelioma cells more susceptible to the lethal effects of standard chemotherapy.

The Research Study

Between 2011 and 2013, the research team used immunohistochemistry tests to determine which of the 201 mesothelioma patients were ASS1-deficient.

Those 68 mesothelioma cases were then divided into those who would receive both an arginine-lowering drug and best supportive care and those who would receive only best supportive care.

After four months of weekly doses of the arginine-lowering drug, more than half of the group that was receiving both therapies experienced stability in the progress of their mesothelioma. Only 22 percent of the group receiving only best supportive care had stable mesothelioma progression.

Just as importantly, the number of patients who had a serious reaction to the treatment was only slightly higher in the two-drug group (25%) than it was in the best supportive care-only group (17%).

“Targeting arginine is safe and warrants further clinical investigation in arginine-dependent cancers,” writes lead author Peter W. Szlosarek, MD, PhD, of the Center for Molecular Oncology at Queen Mary University of London.

Mesothelioma impacts an estimated 2,500 new patients in the US each year and many more around the globe. Most mesothelioma patients have worked in an industry where they were unknowingly exposed to asbestos dust.

Source:

Szlosarek, P, et al, “Arginine deprivation with pegylated arginine deiminase in patients with argininosuccinate synthetase 1-deficient malignant pleural mesothelioma”, September 1, 2016, JAMA Oncology, Epub ahead of print