Beyond the flask: cancer cell lines and the limits of biological extrapolation.

Abstract

Purpose: Cancer cell lines remain central to cancer biology, drug screening, molecular pharmacology, and mechanistic research because they are accessible and experimentally manageable. Their routine use, however, can blur an important distinction between what a model demonstrates directly and what can reasonably be inferred from it. This Editorial examines that boundary and considers how cancer cell lines should be matched to the biological question being asked.

Current concept: Authentication, mycoplasma testing, and careful documentation of culture conditions are essential components of technical validity, but they do not, by themselves, establish biological relevance. A cancer-derived cell line may be entirely appropriate for a focused mechanistic question while providing a much weaker basis for claims about normal tissue physiology, systemic toxicity, tumor-microenvironment interactions, or clinical response. The central issue is therefore not whether cancer cell lines should be used, but whether the model, the research question, and the intended level of inference are aligned.

Conclusion: Cancer cell lines should remain part of the experimental toolkit, but the limits of the evidence they provide need to be stated more clearly. Broader biological or translational claims require broader support from complementary models when the question demands it. Model selection should therefore be driven by the question under study, and conclusions should remain proportionate to what the experimental system can actually support.