From the Hallmarks of Cancer to the Survival System: A Paradigmatic Reconstruction of Oncological Theory through the Existential Crisis-Driven Survival (ECDS) Framework

TL;DR

This paper introduces the ECDS framework, a unifying theory that reinterprets tumor behavior through existential stability and survival capacity, aiming to improve understanding and treatment of cancer heterogeneity and resistance.

Contribution

It proposes the ECDS theory, integrating core oncological concepts into a cohesive framework that explains tumor evolution, heterogeneity, and resistance from an existential perspective.

Findings

Reinterprets the 14 cancer hallmarks within the ECDS framework

Explains the redundancy of survival pathways in tumor heterogeneity

Unveils the 'hierarchical leap' in therapeutic resistance

Abstract

Malignant tumors exhibit complex pathogenesis, yet classical oncological theories remain fragmented, failing to provide a unifying framework to address this complexity. This gap limits the utility and translational potential of the prevailing "confront-and-eradicate" therapeutic paradigm, constraining transformative therapeutic breakthroughs and driving the emergence of acquired and recurrent drug resistance. Here, we propose the Tumor Existential Crisis-Driven Survival (ECDS) theory, anchored in the core proposition that impairment of Existential Stability drives the compensatory hyperactivation of Survival Capacity. This framework defines three foundational constructs (Existential Stability, Survival Capacity, and Existence Threshold) and three guiding principles, unifying and integrating canonical core theories of tumorigenesis. It delineates the dynamic coupling between declining Existential Stability and escalating Survival Capacity during tumor evolution, reinterprets the hierarchical activation of the well-established 14 cancer hallmarks, elucidates the redundancy of survival signaling pathways that underpins intratumoral and intertumoral heterogeneity, and unravels the "hierarchical leap" in therapeutic resistance. By reframing tumors as "Existential Stability erosion-driven passive survival systems" rather than "intrinsically aggressive cellular aggregates", ECDS challenges prevailing dogma, uncovers tumors' intrinsic vulnerability, and establishes a robust meta-theoretical foundation for both basic cancer research and translational clinical management.