The Hallmarks of Cancer as Eco-Evolutionary Processes

Abstract The “Hallmarks of Cancer” represent characteristics of neoplastic cells. Hanahan and Weinberg noted that the acquisition of these hallmarks mimics Darwinian evolution. In this study, we deconstruct the hallmarks “color wheel” into linear, parallel, and interlinked stages: cancer initiation, evolving evolvability, niche construction, adaptations for safety, and emergent phenomenon. During carcinogenesis, a cell evolves from being part of the organism into an autonomous unit subject to natural selection. The hallmark traits enable this transition, representing adaptations for survival within their tumor ecosystem. Unwinding the hallmarks color wheel and viewing them as eco-evolutionary processes provide a unifying framework for defining, understanding, and treating cancer. Significance: Viewing the hallmarks as a sequence of adaptations captures the “why” behind the “how” of the molecular changes driving cancer. This eco-evolutionary view distils the complexity of cancer progression into logical steps, providing a framework for understanding all existing and emerging hallmarks of cancer and developing therapeutic interventions.