The genetic complexity of common cancers and the promise of personalized medicine: is there any hope?

Molecular characterization of frequent cancers has shown that these entities actually include a very large number of rare genomic diseases. The progression of each of these rare diseases is being driven by specific genomic alterations, leading to abnormal proteins that can be targeted. Based on this observation, several personalized medicine programmes have been launched. They consist in profiling the tumour samples from each patient, identifying key oncogenic drivers, and treating the patient accordingly. Several preliminary data suggest that this approach is feasible and could lead to anti-tumour effects that are currently modest. Several reasons could explain why personalized medicine programmes only report modest activity to targeted agents. First, the identification of key oncogenic drivers among several genomic alterations can be challenging. Second, the intratumour heterogeneity could lead to the emergence of resistant clones. Finally, several genomic alterations could contribute to cancer progression. These observations are leading to the second generation of personalized medicine trials, where targeted therapies are combined with each other and with immunotherapeutics, and where patients are selected to present a tumour with a low level of genetic instability.