Organoids cannot replace physiology in cancer drug development

Area of Science:

• Oncology
• Toxicology
• Pharmacology

Background:

• Regulatory agencies are promoting new approach methodologies (NAMs) for cancer drug development.
• The efficacy of NAMs in replacing traditional animal studies is under scrutiny.
• Context-specific application of NAMs is crucial for their acceptance.

Purpose of the Study:

• To evaluate the capabilities and limitations of NAMs in cancer drug development.
• To determine which aspects of drug development can be addressed by NAMs.
• To identify areas where traditional animal studies remain essential.

Main Methods:

• Review of current literature on organoids, organs-on-chips, and computational models in preclinical cancer research.
• Analysis of regulatory guidelines and scientific consensus on NAMs.
• Comparison of data generated by NAMs versus animal models for specific endpoints.

Main Results:

• Organoids, organs-on-chips, and computational models can effectively address localized questions regarding drug efficacy and mechanism of action.
• These NAMs show potential for replacing animal studies in specific, well-defined contexts.
• Assessing whole-body parameters such as biodistribution, immune response, organ clearance, chronic toxicity, and therapeutic index still necessitates integrated physiological evidence, often from animal models.

Conclusions:

• NAMs offer valuable tools for specific applications in cancer drug development, accelerating research and potentially reducing animal use.
• A hybrid approach, combining NAMs with targeted animal studies, is likely the most effective strategy for comprehensive drug evaluation.
• Further validation and standardization of NAMs are required to expand their regulatory acceptance for complex physiological assessments.