Leukemia Drugs for Lung Cancer?

By Cari Wade Gervin
Monday, November 2, 2020

Two recently approved treatments show promise in a new study.

A new study may hold hope for patients with treatment-resistant non-small cell lung cancer.

According to the research, which was published in the journal Nature Chemical Biology, two drugs approved by the FDA for leukemia treatment — gilteritinib and midostaurin — show potential for treating patients who have lung cancer with triple mutant epidermal growth factor receptor (EGFR).

“Patients that present with this mutation don’t have any other options at this point, aside from standard chemotherapies,” says Punit Saraon, PhD, a research fellow at the Ontario Institute for Cancer Research who was the lead author on the study.

Lung cancer is the leading cause of death due to cancer worldwide, and 85% of cases are non-small cell lung cancer. Depending on ethnicity, 15%–50% of those patients have mutations in EGFR, and drug resistance happens in about half of the patients treated with second-generation inhibitors. If the two drugs work in clinical trials, 60,000 to 100,000 patients across the world could benefit.

“In the epidermal growth factor receptor, lung cancer tumors are reliant on this specific kinase,” Saraon says. “These compounds, we show, are able to bind to this specific mutation of this protein. They are also shown to bind to other kinases with different affinities, … but they’re very strong towards this mutation in particular.”

The study tested 3,000 approved drugs on the mutations using a new method called Mammalian Membrane Two-Hybrid Drug Screen—or MaMTH-DS. The technology allows researchers to test molecules directly in living cells and see how they interact with cellular proteins.

“We have a technology that allows us to screen for pretty much any membrane protein now,” Saraon says. “And a lot of membrane proteins are oncogenic in nature in multiple cancers.”

The study also identified molecule EMI1, that has a different way of disrupting the activity of the triple mutations. Instead of inhibiting kinase activity, the molecule targets the receptor for degradation.

“This molecule may be of greater relevance because a lot of these kinase inhibitors result in resistance,” Saraon says. “Maybe this ... could offset this resistance issue. That’s something we’re currently exploring.”

Saraon says his team is currently conducting research on the new compound to alter the chemistry to find its most effective form in possibly shrinking tumors.

“Our goal is now to improve this molecule and understand its mechanism and action to see if it has any therapeutic efficacy in animal models,” Saraon says.