Eradicating Metastatic Cancer and the Eco-Evolutionary Dynamics of Anthropocene Extinctions

Abstract

Curative therapy for metastatic cancers is equivalent to causing extinction of a large, heterogeneous, and geographically dispersed population. Although eradication of dinosaurs is a dramatic example of extinction dynamics, similar application of massive ecoevolutionary force in cancer treatment is typically limited by host toxicity. Here, we investigate the evolutionary dynamics of Anthropocene species extinctions as an alternative model for curative cancer therapy. Human activities can produce extinctions of large, diverse, and geographically distributed populations. The extinction of a species typically follows a pattern in which initial demographic and ecological insults reduce the size and heterogeneity of the population. The surviving individuals, with decreased genetic diversity and often fragmented ecology, are then vulnerable to small stochastic perturbations that further reduce the population until extinction is inevitable. We hypothesize large, diverse, and disseminated cancer populations can be eradicated using similar evolutionary dynamics. Initial therapy is applied to reduce population size and diversity and followed by new treatments to exploit the eco-evolutionary vulnerability of small and/or declining populations. Mathematical models and computer simulations demonstrate initial reductive treatment followed immediately by demographic and ecological perturbations, similar to the empirically derived treatment of pediatric acute lymphocytic leukemia, can consistently achieve curative outcomes in nonpediatric cancers. Significance: Anthropocene extinctions suggest a strategy for eradicating metastatic cancers in which initial therapy, by reducing the size and diversity of the population, renders it vulnerable to extinction by rapidly applied additional perturbations.

Optimal control to reach eco-evolutionary stability in metastatic castrate-resistant prostate cancer

“…Furthermore, delaying the absolute growth of disease within a patient could allow other physiological processes, such as vascular normalization and the immune system, that have little effect on large rapidly growing tumors to play a greater role in patient outcomes [33]. It is also possible that curative strategies using application of additional drugs or immune therapies could be more effective in a stabilized tumor environment [67][68][69][70][71][72][73][74].…”

The contribution of evolutionary game theory to understanding and treating cancer

“…. Here v i denotes the treatment-induced resistance to treatment i, r is the intrinsic growth rate of the tumor cells, and (6) to analyze possible strategies to combat the pediatric sarcoma, motivated by the theory of extinction from ecology, recently discussed in the oncology literature as well [74,68].…”

Insights From the Ecology of Information to Cancer Control

“…In this commentary, we argue that these results provide potential insights into novel strategies for controlling cancer within the context of eco-evolutionary dynamics of Anthropocene extinctions. 6…”

“…We see parallels between Schmidt’s 4 model of the effects of environmental disturbance on the role of information in extinction vulnerability and a proposed strategy to eradicate cancer based on Anthropocene extinctions. 6,21 The essence of this strategy is to apply a sequence of powerful and effective chemotherapies in quick succession. Better yet, this strategy can be extended to targeted agents and immunotherapies, as well as combinations of both with chemotherapy.…”

“…22,23 In many Anthropocene extinctions, human persecution (eg, overhunting) drove a species to small and fragmented subpopulations, and a later environmental or demographic perturbation subsequently eliminated the last remaining vestiges of the species, resulting in global extinction. 6 By analogy, the “First Strike–Second Strike” strategy would take advantage of the reduction in size and diversity of dispersed cancer populations following an initial application of a cancer drug at maximum tolerated dose by a rapid application of a “second strike” application of an alternative cancer drug that works with a different mode of action. Schmidt’s 4 model suggests that 1-second tactic might come in the form of chemotherapies that preclude surviving cancer cells from gaining information about their surrounding microenvironment.…”