Pemetrexed (Alimta) was approved by the FDA in 2004 and remains the only drug specifically approved for the treatment of mesothelioma, a virulent cancer closely linked to asbestos exposure.
Although pemetrexed is the most common drug treatment for mesothelioma, it is far from universally effective. In fact, only about 4 out of 10 mesothelioma patients will benefit from treatment with pemetrexed.
Boosting Mesothelioma Chemotherapy
One reason pemetrexed has such difficulty killing mesothelioma cells is that several cell lines of the cancer are resistant to its damaging effects. Overexpression of a particular enzyme called thymidylate synthase (TS) has been linked to this resistance.
This week, a new study conducted at Italy’s University of Torino finds that a drug normally used to treat leukemia has the potential to extend mesothelioma survival by enhancing the cancer-killing power of pemetrexed.
The drug, called dasatinib (Sprycel), is a targeted therapy that inhibits certain tyrosine kinases, enzymes that play a critical role in the growth and proliferation of cancer cells. Produced by Bristol-Myers Squibb, dasatinib is approved for first line treatment of people with chronic myelogenous leukemia and acute lymphoblastic leukemia.
Testing Dasatinib as a Mesothelioma Treatment
To determine whether dasatinib could be a helpful addition to mesothelioma chemotherapy treatment, University of Torino researchers exposed three different mesothelioma cell lines to pemetrexed alone, dasatinib alone, one right after the other, or a combination of the two drugs.
After each treatment approach, the researchers tested the viability of the mesothelioma cells, the rate of apoptosis (cell death) and migration, TS expression and other parameters.
“Dasatinib treatment impaired cells migration, and both sequential and co-administration with PEM [pemetrexed] significantly increased apoptosis,” reports research study author Dr. Valentina Monica, an oncologist with San Luigi Hospital at the University of Torino. ”These data indicate that dasatinib sensitizes mesothelioma cells to pemetrexed through TS downregulation.”
If the results of this targeted mesothelioma therapy approach can be confirmed in subsequent studies, it could be good news for the 2,500 Americans diagnosed with the asbestos cancer each year. Even with the most advanced mesothelioma therapies currently known, including pemetrexed-based chemotherapy, the odds of long term mesothelioma survival remain low.
Monica, V, et al, “Dasatinib modulates sensitivity to pemetrexed in malignant pleural mesothelioma cell lines”, July 6, 2016, Oncotarget, Epub ahead of print