Transient IGF-1R inhibition combined with osimertinib eradicates AXL-low expressing mutated lung cancer

How some lung cancer cells develop drug resistance

15 January 2021

The discovery of how certain lung cancer cells become resistant to one of the most effective drugs available could lead to improved therapies for the disease.

Globally, lung cancer claims more lives than any other cancer. Drugs that target specific genetic mutations that drive the disease are effective, but often they only buy patients time because tumours develop resistance to them.

Now, a team led by researchers at Kanazawa University in Japan has discovered how certain lung cancer cells with mutations to the gene that encodes for a protein called epidermal growth factor receptor (EGFR) develop resistance to the drug osimertinib.

Although EGFR-mutated lung cancer cells that express low amounts of the protein AXL are initially sensitive to osimertinib, a few cells survive treatment with the drug, giving rise to drug-resistant tumours. The researchers identified the genetic basis for this resistance.

This knowledge will help to develop combination treatments that could be much more effective than treatment by osimertinib alone.

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References

1. Nature Communications 11, 4607 (2020). doi: 10.1038/s41467-020-18442-4