A new perspective on tumor progression: Evolution via selection for function

Abstract

Tumorigenesis is commonly attributed to Darwinian processes involving natural selection among cells and groups of cells. However, progressing tumors are those that also achieve an appropriate group phenotypic composition (GPC). Yet, the selective processes acting on tumor GPCs are distinct from that associated with classical Darwinian evolution (i.e. natural selection based on differential reproductive success) as tumors are not genuine evolutionary individuals and do not exhibit heritable variation in fitness. This complex evolutionary scenario is analogous to the recently proposed concept of 'selection for function' invoked for the evolution of both living and non-living systems. Therefore, we argue that it is inaccurate to assert that Darwinian processes alone account for all the aspects characterizing tumorigenesis and cancer progression; rather, by producing the genetic and phenotypic diversity required for creating novel GPCs, these processes fuel the evolutionary success of tumors that is dependent on selection for function at the tumor level.

Keywords: evolution; function; group phenotypic composition; perspective; progression; selection; tumors.

Figure 1.

Nested selective processes are responsible for the long-term evolutionary success of a tumor. The example above represents progression toward a malignant tumor, but as indicated in the main text, this is not necessarily the only possible scenario. (A) The first stages of tumorigenesis are driven by Darwinian processes among individual cells and clusters of cells. (B) These Darwinian processes also constantly and dynamically generate variable GPCs in the tumor. (C) The generation of variable GPCs propels the tumor into a second dynamic characterized by selection for function, in which tumor growth occurs when there is alignment between the tumor’s functionality (as defined by Wong et al. [7]) induced by the GPC and the current microenvironment. Unraveling these two evolutionary dynamics and the mechanisms that drive them is essential for fully understanding tumorigenesis. Figure adapted from Capp et al. [5].