Clinical and translational relevance of intratumor heterogeneity.

Intratumor heterogeneity (ITH) is a driver of tumor evolution and a main cause of therapeutic resistance. Despite its importance, measures of ITH are still not incorporated into clinical practice. Consequently, standard treatment is frequently ineffective for patients with heterogeneous tumors as changes to treatment regimens are made only after recurrence and disease progression. More effective combination therapies require a mechanistic understanding of ITH and ways to assess it in clinical samples. The growth of technologies enabling the spatially intact analysis of tumors at the single-cell level and the development of sophisticated preclinical models give us hope that ITH will not simply be used as a predictor of a poor outcome but will guide treatment decisions from diagnosis through treatment.
Competing Interests: Declaration of interests K.P. serves on the Scientific Advisory Board of Novartis, Vividion Therapeutics, Ideya Biosciences, and Scorpion Therapeutics, holds equity options in Scorpion Therapeutics, received honoraria from Astra-Zeneca, New Equilibrium Biosciences, and Roche in the past 12 months, and receives sponsored research funding from Novartis. The remaining authors have no interests to declare.
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