Clonal Heterogeneity and Tumor Evolution: Past, Present, and the Future

Publication date: 9 February 2017
Source:Cell, Volume 168, Issue 4
Author(s): Nicholas McGranahan, Charles Swanton
Intratumor heterogeneity, which fosters tumor evolution, is a key challenge in cancer medicine. Here, we review data and technologies that have revealed intra-tumor heterogeneity across cancer types and the dynamics, constraints, and contingencies inherent to tumor evolution. We emphasize the importance of macro-evolutionary leaps, often involving large-scale chromosomal alterations, in driving tumor evolution and metastasis and consider the role of the tumor microenvironment in engendering heterogeneity and drug resistance. We suggest that bold approaches to drug development, harnessing the adaptive properties of the immune-microenvironment while limiting those of the tumor, combined with advances in clinical trial-design, will improve patient outcome.

Teaser

Cancer cells interact with each other and with the microenvironment, fostering tumor diversity and evolution. This Review discusses the etiology and clinical implications of intra-tumor heterogeneity and outlines novel therapeutic approaches that account for tumor diversity and evolution.


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