An opinion article in Trends in Biotechnology by João Conde, a nanomedicine and clinical oncology researcher at EARA member NOVA Medical School in Portugal, argues that organoids cannot replace physiology in cancer drug development. 

New approach methodologies (NAMs), including organoids, organs-on-chip and computational models, can answer more localised questions in specific cancer cells, such as how drugs interact with a specific target and provide early indication of efficacy. Yet they cannot answer questions that require interaction between organs, including how drugs distribute in the body, are eliminated, interact with the immune system, and affect toxicity and therapeutic potential. 

As regulators around the world, namely in the European Union, UK, US and Japan, are accelerating the use of NAMs to develop new cancer drugs, their capacity to replace animals greatly depends on the context of use for each NAM. “The global convergence is therefore not ‘organoids instead of animals’, but validated human-relevant evidence, used in a clearly defined context of use,” wrote João Conde, who compiled a table of NAMs that can and cannot replace and reduce animal studies in different contexts of cancer drug development. The researcher argues that NAMs should declare the context for which they are intended, for example, a NAM can be used to assess how a drug acting directly in cancer cells can induce their death. The context should be declared before making any claims of replacement and should be reproducible and thoughtfully compared using well-characterised drugs and human historical data. 

“The goal is not to eliminate animal studies but to replace low-value animal testing and avoid unvalidated NAM use. Progress will come from context-of-use validation, applying NAMs where they are strongest and reserving animal studies for systemic physiology that cannot yet be replicated,” concluded the researcher.