Life History Trade-Offs in Tumors

Abstract

Purpose: In this paper, we provide an overview of a life history theory and how it applies to cancer evolution.

Recent findings: We review the literature on trade-offs in tumors, focusing on the trade-offs among cellular proliferation, survival, and motility. Trade-offs are critical natural constraints for almost all evolutionary processes. Many ecological studies show that trade-offs among these cellular functions maintain a genetic diversity. In addition, these trade-offs are not fixed, but rather can shift depending on the ecological circumstances in the microenvironment. This can lead to selection for the cellular capacity to respond to these differing microenvironments in ways that promote the fitness of the cancer cell. We relate these life history trade-offs to the recently developed Evo-Eco indexes and discuss how life history theory can help refine our measures of tumor evolution and ecology.

Summary: Life history theory provides a framework for understanding how the spatial and temporal variability in the tumor microenvironment-in particular resources and threats-affect trade-offs among cell survival, cell proliferation, and cell migration. We discuss how these trade-offs can potentially be leveraged in cancer therapy to increase the effectiveness of treatment.

Keywords: Cancer evolution; Ecology; Evolutionary theory; Life history trade-offs; Neoplastic progression.

Fig. 1

Dynamical trade-offs between two traits of cells under evolutionary processes. When two traits of tumor cells, e.g., growth (y-axis) and resistance to drug or ability to escape immune cell attack (x-axis) have a trade-off, the tumor cells evolve inside the gray area in the trait space. The improvement of resistance (trait 2) will lead to a cost of growth (trait 1). The shape of the trade-offs can be classified as linear, concave (initially weak and cheap trade-off), or convex (initially strong and costly trade-off) compared to the linear shape. It is critical for the diversity level of a tumor population. Tumor cells do not necessarily evolve along a trade-off curve with one specific shape. Instead, it is a dynamical process. For example, if the immune cells improve their ability to attack the tumor cells, the cost of the tumor cells to escape immune cells can increase over time, i.e., the tumor cells jump from an initially weaker (cheaper) trade-off curve to a stronger (more costly) one. This kind of dynamical trade-offs has been observed in bacteria populations when the bacteria cells evolve to escape the predation of ciliates