Toward understanding and exploiting tumor heterogeneity

Abstract

The extent of tumor heterogeneity is an emerging theme that researchers are only beginning to understand. How genetic and epigenetic heterogeneity affects tumor evolution and clinical progression is unknown. The precise nature of the environmental factors that influence this heterogeneity is also yet to be characterized. Nature Medicine, Nature Biotechnology and the Volkswagen Foundation organized a meeting focused on identifying the obstacles that need to be overcome to advance translational research in and tumor heterogeneity. Once these key questions were established, the attendees devised potential solutions. Their ideas are presented here.

Figure 1

Herrenhausen Palace. Image credit: Eberhard Franke for Volkswagen Foundation.

Figure 2

The clonality of tumor evolution. In tumor evolution, driver alterations may result in the formation of the initial tumor clone. As further driver alterations occur, these clones then branch off to form subclones. Founder mutations that occur in the original tumor clone are hard to identify, however, as a mutation at point (1) may be considered to be a founder mutation, but further mutations at point (2) would have been considered to be in the initial clone had the sample at point 1 not been taken.

Figure 3

Influences on cancer cell state. The cancer cell state is representative of the genetic and epigenetic components as well as the signaling environment, which collectively determine which genes are expressed by the cell. These properties may be altered by subclonal evolution and can influence the initiation, progression and drug response of the tumor, affecting both the bulk tumor and the single-cell state. The gray arrows show the timescales of these processes and the factors that might influence cell state on each timescale are indicated.