The hybrid preclinical ecosystem: a strategic roadmap for oncology R&D.

Abstract

Regulatory shifts, economic pressures, and pandemic-related logistical disruptions have challenged the long-standing primacy of animal models in biomedical research. In oncology, the traditional "animal-first" paradigm is increasingly difficult to defend as advances in human-derived systems-including tumor organoids, microphysiological systems, and computational models-now enable the study of specific aspects of tumor biology in experimentally controlled and human-relevant contexts. Consequently, the conceptual architecture of preclinical research is being reorganized; rather than suggesting a replacement of animal models, these changes point to a gradual reconfiguration of how different model systems are positioned within the translational pipeline. This shift necessitates a fundamental reassessment of how experimental design translates into clinical relevance. A strategic roadmap for this hybrid ecosystem illustrates how the integration of human-specific data and refined animal validation can de-risk clinical translation in oncology.