Quinacrine for Mesothelioma? Anti-Malaria Drug May Help Patients with This Gene Mutation

Another study on quinacrine for mesothelioma suggests that the once-popular anti-malaria drug might help a subset of patients with a particular gene mutation.

Quinacrine is sold under the brand name Atabrine. It used to be the main anti-malaria drug but most doctors now prefer chloroquine. 

Last fall, Penn State research on quinacrine for mesothelioma showed the drug has a “high degree of cytotoxicity” on its own.

The newest study initially focused on the potential for synergistic effects of quinacrine and chemotherapy. It turns out that the drug can make cisplatin more lethal to mesothelioma cells. Further tests showed that cells with inactivated NF2 mutations were even more sensitive to quinacrine. As many as 60 percent of mesothelioma patients may have this mutation.

Why Scientists are Hopeful About Quinacrine for Mesothelioma

Quinacrine is a drug with many uses. Although doctors no longer use it to prevent malaria, they do use it to treat giardiasis, a diarrheal disease caused by a parasite. It has also been used to treat rheumatoid arthritis and lupus. 

Cancer doctors do not usually think of quinacrine for mesothelioma treatment. But last year’s study showed it killed both lab-grown and patient-derived mesothelioma cell lines. It was effective even at a very low dose. 

That study brought to light some qualities of quinacrine that might make it a good possibility for mesothelioma. When scientists applied it to mesothelioma cells, it kept them from forming colonies. 

It can also keep tumors from forming new blood vessels (angiogenesis). It inhibits autophagy, a process that helps cancer cells survive by “recycling” old parts. And it triggers the natural cell death process called apoptosis. 

Mutated Gene Sensitizes Mesothelioma Cells

Researchers at the Mayo Clinic and the University of California conducted the newest quinacrine study. They noted that there are few good treatment options for mesothelioma patients. One reason is that only about 40 percent of mesothelioma tumors respond to chemotherapy.

The two main chemotherapy drugs for mesothelioma are pemetrexed (Alimta) and cisplatin. So the Mayo Clinic and UC researchers tried combining each drug with quinacrine for mesothelioma cell treatment. 

“The combination with cisplatin resulted in synergistic cell death and the combination with pemetrexed was not synergistic,” they report. 

But they also made an unexpected discovery. They found that mesothelioma cells with mutations on the NF2 gene were extra sensitive to quinacrine. 

“There are few common mutations in mesothelioma and inactivating NF2 mutations are present in up to 60% of these tumors,” writes lead researcher Derek Oien of the Mayo Clinic. “This study suggests quinacrine may have repurposing potential for a large subset of mesothelioma patients.”

More testing will need to be done before quinacrine for mesothelioma becomes mainstream. The good news is that quinacrine is already an FDA-approved drug. If more studies show it works, doctors could start using it quickly.

Source:

Oien, D, et al, “Quinacrine Has Preferential Anticancer Effects on Mesothelioma Cells With Inactivating NF2 Mutations”, September 21, 2021, Frontiers in Pharmacology, eCollection, https://www.frontiersin.org/articles/10.3389/fphar.2021.750352/full