Cancer drugs that target specific proteins overproduced because of a genetic abnormality may also be effective in patients whose tumours lack that abnormality.

Jeff Settleman at Genentech in South San Francisco, California, and his team found a molecular marker in some cancers that could pinpoint patients likely to respond to drugs targeting HER2 — a protein overexpressed in about 25% of breast cancers — even though the HER2 gene in their tumours functions normally.

The researchers identified a number of such tumours, many of them head and neck cancers, in a screen of 690 tumour cell lines. Further experiments found that these tumours are driven by a boost in the protein neuregulin-1, which activates HER2 indirectly by switching on its sister protein, HER3. The HER2 inhibitor lapatinib disrupted the pathway in vitro, and suppressed HER2, HER3 and tumour growth in a human cancer cell line engrafted into mice.

Cancer Cell 20, 158–172 (2011)