Abstract Malignant tumors have long been viewed as uncontrolled cell proliferation driven by somatic mutations. However, emerging multi-omics and microenvironment evidence challenges this paradigm. Advanced tumors transcend cellular abnormality to form a “neoorgan” – a complex tissue ecosystem with multicellular coordination, functional autonomy, metabolic symbiosis, neural integration, and evolutionary potential. Genomic instability generates lineage-specific karyotypes; tumors reactivate ancient gene modules from primitive multicellular organisms; they actively remodel immune function via mitochondrial transfer; and they establish functional connections with the nervous system. Based on this evolutionary trajectory, we propose testable predictions: tumors may progress from a parasitic neoorgan toward an independent species, as exemplified by naturally occurring transmissible tumors and the “tumor-derived animal” hypothesis. Recognizing cancer as an evolutionary entity striving for independence – rather than a mere genetic malfunction – demands a fundamental shift in therapeutic strategy. Instead of solely cytotoxic “killing”, rational approaches may aim to reintegrate the tumor into host regulatory networks or guide its evolution toward self-destruction. This framework expands tumor biology and challenges conventional boundaries between disease, life, and species.
Chen et al. (2026) studied this question.