The NCI-60 Human Tumor Cell Line Screen: A Catalyst for Progressive Evolution of Models for Discovery and Development of Cancer Drugs

Following three decades of systematic primary empirical screening against mice bearing two transplantable murine leukemias, the NCI took the bold step of switching to a radically different approach-initial screening of 10,000 diverse compounds/year against a panel of 60 human tumor cell lines in vitro. The establishment of the NCI-60 screen was announced in the landmark Cancer Research article by Alley and colleagues, published in 1988, which exemplified the technological basis for the new microculture screen, operating at unprecedented scale. The underlying concept was that NCI-60 might expedite the discovery of innovative cancer drugs, especially those with predicted activity against particular solid cancers-not then possible. We discuss how NCI-60 provided a major technological advance and delivered a successful legacy for cancer research and development. While not immediately cracking the thorny problem of model-to-human tumor type prediction, NCI-60 nevertheless provided the conceptual and methodologic foundation for subsequent, much larger-scale human cancer cell panel screens with detailed molecular annotation and sophisticated informatics. Now used in modern molecular target-based drug discovery, these panels help enable the implementation of contemporary biomarker-led precision oncology.

Automated summary

The NCI-60 screen, which involved screening of 10,000 diverse compounds against 60 human tumor cell lines, marked a major technological advance in cancer research and development. It provided the foundation for subsequent larger-scale human cancer cell panel screens with detailed molecular annotation and sophisticated informatics, enabling the implementation of modern molecular target-based drug discovery and precision oncology.