Figure 1. Intratumor heterogeneity and clonal evolution.

Adapted from Jamal-Hanjani M, Quezada SA, Larkin J, Swanton C. Translational implications of tumor heterogeneity. Clin Cancer Res 2015; 21: 1258-1266, with permission from AACR [34]. Primary tumors consisting of different subclones may be subjected to various selection pressures (e.g. chemotherapy, and micro-environmental factors such as hypoxia, and infiltrating stromal and immune cells). Under the influence of selection pressures, subclones with intrinsic resistance (green) can outgrow a tumor mass, potentially leading to disease progression, and/or can acquire somatic alterations (purple) promoting cell survival, proliferation, and metastatic tumor formation. The outgrowth of some subclones (red) may be constrained by selection pressures that they are sensitive to; for example, targeted therapy against a tumor subclone with a somatic alteration sensitive to therapy.