(NEJM, 2016)
By John Hickman and Ian Tannock
This commentary addresses some of the reasons for the limited impact of cancer drugs targeted to the genetic lesions driving malignancies. The genetic heterogeneity of advanced cancers is a particular barrier to the effective use of single targeted therapies because there are multiple genetic drivers. The paper reviews some of the data on the use of drug combinations that attempt to overcome the challenge of genetic heterogeneity, suggesting that drug combinations are limited by significant host toxicity. In particular, the paper questions the growing use of targeted drugs guided by the next generation sequencing of tumour genomes, in so-called precision or personalised medicine trials. It asks that this approach is only taken as part of well-controlled trials and that patients should be informed of the limits of personalised cancer medicine with targeted therapies.