Resistance in targeted cancer therapy

A therapeutic target that may prevent or overcome the acquired resistance to treatment seen in non-small cell lung cancers (NSCLC) harboring a specific gene mutation is reported this week in Nature Genetics.

Treatment of NSCLC that have a mutation in the cell surface receptor EGFR with tyrosine kinase inhibitors, such as erlotinib, extends life by an average of about three months. However, with this treatment, tumors almost always acquire resistance.

Trever Bivona and colleagues show that the enzyme AXL kinase is upregulated in some resistant human NSCLC. They further showed that inhibiting AXL function in cell and mouse models of resistant tumors restored sensitivity to the common NSCLC drug erlotinib. The authors suggest AXL as a therapeutic target that for patients with acquired resistance in EGFR-mutant lung cancer.