Variable Clonal Repopulation Dynamics Influence Chemotherapy Response in Colorectal Cancer

Abstract

Dissecting Diversity Solid tumors are composed of functionally diverse tumor cells. The prevailing view is that this "intratumoral heterogeneity" arises from the accumulation of mutations during tumor growth, resulting in multiple genetically defined subclones of cells that respond in different ways to selective pressures such as chemotherapy. Kreso et al. (p. 543 , published online 13 December; see the Perspective by Marusyk and Polyak ) simultaneously monitored the genetic profiles and growth behavior of human colorectal cancer cells that were serially passaged in mice. Individual tumor cells within a uniform genetic lineage displayed extensive variation in survival, growth dynamics, and response to a chemotherapeutic drug. Thus, additional diversity-generating mechanisms such as epigenetic regulation or microenvironmental variability appear to operate within a genetic clone, endowing a subset of tumor cells with robust survival potential, especially during stress.