Issue link: https://viewer.e-digitaledition.com/i/1305733
Lung Cancer? Leukemia Drugs for Lung Cancer? BY CARI WADE GERVIN T WO RECENTLY APPROVED TRE ATMENTS SHOW PROMISE IN A NE W 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 muta- tion don't have any other options at this point, aside from standard chemothera- pies," 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-gener- ation 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 recep- tor, 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 a lso 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 ca lled Ma mma lia n Membra ne 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 st udy a lso i de nt i f i e d molecule EMI1, that has a different way of disrupting the activ- it y of the triple mutations. Instead of inhibiting kinase activity, the molecule ta rgets the receptor for deg radation. " T h i s molecu le m ay be of g reat er releva nce because a lot of these kinase inhibitors result in resista nce," Saraon says. " Maybe this ... cou ld of fset this resistance issue. That's something we're currently exploring." Saraon says his team is currently con- ducting research on the new compound to alter the chemistry to find its most effec- tive form in possibly shrinking tumors. "O u r goa l i s now t o i mprove t h i s molecu le a nd understa nd its mecha- n i sm a nd a c t ion t o see i f it h a s a ny therapeutic eff icacy in anima l models," Sa raon says. n M D N E W S . C O M /// M D N E W S G R E AT E R K A N S A S ■ 2 0 2 0 C L I N I C A L D I S C U S S I O N ❰❰❰❰❰ 0 5