ALK inhibitor may treat ALK-negative cancers?

Targeted therapy is a newer type of medical treatment for cancer. It blocks cancer cell growth by targeting specific molecules needed for cancer development and progression. Since targeted therapy can more precisely identify and attack cancer cells, it tends to be more effective and have fewer side effects than traditional chemotherapy.

According to a study published online 9 Oct. 2017 in Nature Chemical Biology, the targeted therapy ceritinib, which is an ALK inhibitor, can block the growth of ALK-negative lung cancer cells. The study also uncovers several novel targets of the drug. These findings extend our understanding of how ceritinib works and may broaden the drug's application in cancer treatment since the drug is currently used in the treatment of ALK-positive cancer.

The cost of developing a new drug, from research and development to marketing approval, is extremely high and likely to grow even higher. Drug development often takes more than 10 years, and there is a risk of failure. Another strategy is drug repurposing -- using known drugs to treat new diseases. The advantages of drug repurposing are that it costs much less and has a lower risk of failure.

To uncover new therapeutic opportunities for known drugs, researchers from H. Lee Moffitt Cancer Center and Research Institute employed an integrated phenotypic screening, chemical and phosphoproteomics strategy. This method allowed them to effectively analyzed hundreds of FDA-approved drugs and experimental drugs. They discovered that the ALK inhibitor ceritinib showed activity in several ALK-negative lung cancer cell lines.

Further investigation revealed that the working mechanism of ceritinib involves the noncanonical targets IGF1R, FAK1, RSK1 and RSK2. Moreover, combining ceritinib with a second chemotherapy medication called paclitaxel led to enhanced therapeutic efficacy. Collectively, these data indicate that ceritinib may be used to treat cancer without ALK rearrangements.

This work emphasizes the potential of ceritinib repurposing as a novel way to find cancer treatments. The strategy the researchers used in this work to identify previously unknown targets of ceritinib presents a useful approach to understand the mechanism of action of targeted therapies and to design novel drug combinations.
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