The coming decade in precision oncology: six riddles

High-throughput methods to investigate tumour omic landscapes have quickly catapulted cancer specialists into the precision oncology era. The singular lesson of precision oncology might be that, for it to be precise, treatment must be personalized, as each cancer’s complex molecular and immune landscape differs from patient to patient. Transformative therapies include those that are targeted at the sequelae of molecular abnormalities or at immune mechanisms, and, increasingly, pathways previously thought to be undruggable have become druggable.The host’s role is also likely to be key in determining treatment response, especially for immunotherapy. Indeed, maximizing the impact of immunotherapy will require omic analyses to match the right immune-targeted drugs to the individualized patient and tumour setting. In this Perspective, we discuss six key riddles that must be solved to optimize the application of precision oncology to otherwise lethal malignancies.