Two approved therapeutics for treating leukemia are currently being investigated for treatment-resistant lung cancer. The findings were based on a live cell method developed to identify small molecules that target specific mutations in cancer cells.
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"Drug resistance is a big problem for lung cancer patients," says Igor Stagljar, a professor of molecular genetics and biochemistry at the Donnelly Centre for Cellular and Biomolecular Research. "Our new technology allows us to find molecules that could be used against cancers for which no other treatment options are available."
The drugs used in the study are gilteritinib and midostaurin which have been previously approved to treat a particular form of leukemia. Now, these drugs could treat highly resistant lung cancer patients with triple mutant epidermal growth factor receptor (EGFR).
"We already have a sense of gilteritinib doses that are safe to give to humans," says Dr. Adrian Sacher, an oncologist at Toronto's Princess Margaret Cancer Centre, at University Health Network, who will lead the trial. "We only need to demonstrate efficacy and hopefully make them a novel treatment option for lung cancer patients that have developed resistance to current targeted therapies."
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Findings were published in Nature Chemical Biology.
"The advantage of our method is that we are doing it in living cells, where we have all the other molecular machineries present that are important for signal transduction," says Stagljar. "Also, the compounds are fished at very low dose, which allows us to test for both permeability and toxicity at the same time."
"The unbiased screening approach by the Stagljar's group has the merit of identifying small molecule inhibitors that could act via new mechanisms of action that would otherwise escape detection by conventional drug development strategies, as shown in this proof of principle study, " says Marino Zerial, Managing Director of the Max Planck Institute of Molecular Cell Biology and Genetics in Dresden, Germany and one of Stagljar's collaborators.
Source: Science Daily