New data suggests that doctors might have good luck using a leukemia drug to treat pleural mesothelioma.
The drug in question is ponatinib. It sells under the brand name Iclusig. Ponatinib is a pill that inhibits certain enzymes that may lead to mesothelioma tumor growth.
A study carried out at the University of California showed that the leukemia drug kept mesothelioma cells from growing and spreading in the lab. It could give doctors a new treatment option for patients who do not respond to standard therapies.
How the Leukemia Drug Works
Ponatinib is a tyrosine kinase inhibitor. Tyrosine kinases are enzymes that interact with certain proteins inside cells. Tyrosine kinases act as on/off switches for many cellular functions.
In some kinds of cancer, including leukemia and mesothelioma, certain tyrosine kinases are overactive. This means they may be telling cancer cells to grow quickly and migrate to other parts of the body. Ponatinib blocks this process.
The University of California researchers wanted to know which tyrosine kinases are overactive in mesothelioma cells. Depending on which ones they are, this leukemia drug might be helpful.
Ponatinib blocks multiple tyrosine kinases. If it can block the ones that are overactive in mesothelioma, it might slow the spread of this virulent cancer.
Ponatinib Could Be a New Treatment Option
People with malignant pleural mesothelioma do not have many treatment options. Most people start with chemotherapy. Chemotherapy drugs like Alimta aim to kill mesothelioma cells. But chemotherapy does not always work well for mesothelioma treatment. At best, it may extend life by a few months.
A leukemia drug that blocks growth signaling pathways might get to the heart of the problem. To test the idea, University of California researchers used four different mesothelioma cells lines. All four cell lines showed high levels of two tyrosine kinases. Then, they exposed these cells to ponatinib.
“Differentially but strongly, ponatinib inhibited the in vitro cell growth and migration of all four malignant pleural mesothelioma lines,” writes lead author Yi-Wei Yang in Experimental Lung Research. Cellular levels of a key tyrosine kinase and the proteins that it manages “were markedly decreased following ponatinib treatment.”
The researchers also applied the leukemia drug to a human mesothelioma tumor in a mouse. It slowed the growth of that tumor and reduced the levels of two important tyrosine kinases.
“Ponatinib may offer a new therapeutic strategy for malignant pleural mesothelioma patients based on cAbl signaling pathway inhibition,” the team concludes. Unlike some other experimental mesothelioma treatments, ponatinib is already FDA-approved and readily available.
Other mesothelioma researchers are also exploring tyrosine kinase inhibitors for mesothelioma. In 2016, Canadian researchers found that another leukemia drug called dasatinib (Sprycel) made mesothelioma cells more sensitive to chemotherapy with Alimta.
Yank, YW, et al, “Ponatinib is a potential therapeutic approach for malignant pleural mesothelioma”, October 27, 2020, Experimental Lung Research, Epub ahead of print, https://www.tandfonline.com/doi/abs/10.1080/01902148.2020.1836691?journalCode=ielu20
Monica, V, et al, “Dasatinib modulates sensitivity to pemetrexed in malignant pleural mesothelioma cell lines”, July 6, 2016, Oncotarget, Epub ahead of print