The efficacy of a cancer drug that targets a particular class of mutations depends on the tumour tissue type and the exact nature of the mutation, reports a clinical trial published online in Nature. The research highlights how molecularly driven clinical trials can be used to enhance our understanding of the effects of genetic mutations, a finding that could aid the development of personalized cancer therapies.
Various mutations in the HER2 and HER3 genes are found in a wide range of cancers. Some of these mutations cause overexpression of the HER2 protein, leading to cancer, but most are uncharacterized. David Hyman and colleagues tested the efficacy of neratinib, a drug that blocks the activity of HER proteins, in 141 patients with a variety of cancers, including breast, lung, bladder and colorectal, and a variety of different mutations in the HER2 and HER3 genes. They found that the response to treatment was determined by mutation and tissue type, and was restricted to cancers with HER2 mutants.
The move towards personalized cancer therapies has been hampered because the clinical and biological importance of most genomic variants is unknown. This study helps to change that, providing new insights that were not predicted by preclinical models. It also highlights the value of so-called ‘basket’ trials, which focus on a mutation type, such as those found in the HER genes, rather than the tissue in which the cancer appears.