The coming decade in precision oncology: six riddles

In this Perspective, Wahida et al. consider six riddles in precision oncology that must be solved to achieve better clinical responses to molecular targeted therapies. 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. Critical to applying precision medicine is the concept that the right combination of drugs must be chosen for each patient and used at the right stage of the disease. Multiple puzzles remain that complicate therapy choice, including evidence that deleterious mutations are common in normal tissues and non-malignant conditions. 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.

Automated summary

In this Perspective, the authors discuss six key challenges in precision oncology that need to be addressed in order to improve clinical response to molecular targeted therapies. The core principle of precision oncology is that treatment must be personalized, as each cancer has a unique molecular and immune landscape. Choosing the right combination of drugs for each patient and using them at the appropriate stage of the disease is critical to applying precision medicine.