Malignant mesothelioma is a deadly form of cancer that is notoriously resistant to treatment. Despite the best efforts of researchers and physicians, the asbestos-related disease continues to claim the lives of patients shortly after their diagnosis. Though the gold standard treatment for mesothelioma continues to be a combination of platinum-based chemotherapy along with surgery and radiation therapy, a new discovery by researchers at the University of British Columbia’s faculty of medicine and BC Cancer Research Institute has given rise to new hope for a breakthrough.
Weakness in Enzyme Called “Achilles Heel” of Cancer Tumors Like Mesothelioma
A new study published in the journal Science Advances has given rise to the hope for a new treatment strategy for malignant mesothelioma. The researchers have identified a weakness in a key enzyme found in solid tumor cancer cells. Referring to it as the cells’ Achilles heel, they are hoping that they can leverage the weakness to cause cell death.
Solid tumors like those found in mesothelioma develop blood vessels that supply them with the nutrients and oxygen that they need to grow. When the tumors outgrow the ability of these vessels to provide them with what they need, acid builds up inside of them. But the cells respond to this acid by releasing neutralizing enzymes that end up making the tumors more aggressive and causing them to spread.
Inhibiting Enzyme and Combining with Proteins Causes Cell Death
The researchers found that cancer cells like those in mesothelioma tumors need the enzyme Carbonic Anhydrase IX (CAIX) to survive. Though inhibiting its activity could stop the cells from growing, by using a tool called a genome-wide synthetic lethal screen they determined that an even greater impact was possible by combining a CAIX-inhibiting agent with a gene that causes ferroptosis, a type of catastrophic cell death caused by iron buildup.
According to senior author Dr. Shoukat Dedhar, professor in UBC faculty of medicine’s department of biochemistry and molecular biology and distinguished scientist at BC Cancer, “We now know that the CAIX enzyme blocks cancer cells from dying as a result of ferroptosis. Combining inhibitors of CAIX, including SLC-0111, with compounds known to bring about ferroptosis results in catastrophic cell death and debilitates tumor growth.”
As researchers make inroads in the fight against mesothelioma, those who have been diagnosed with the rare and fatal form of cancer continue to need support and resources. For assistance today, contact the Patient Advocates at Mesothelioma.net at 1-800-692-8608.
