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Last Updated: 06/21/23

Research Paradigm (1990-Present)

Cell tray

Anticancer drugs are tested on human tumor cell lines in vitro for cytotoxicity and effectiveness. Courtesy of NCI. 1989.

Human tumor cell line assay adopted as primary screen

Michael Boyd, M.D., Ph.D.
Former Associate Director, DTP

Video

Boyd Video #1

Video

Boyd Video #2

Transcripts

The human tumor cell line screen represents nine disease types and permits testing of compounds against a broad panel of human tumors.

Since April 1990, DTP has used the human tumor cell line in vitro screen as its primary assay. The screen is currently composed of 59 human tumor cell lines, representing leukemia, melanoma, and cancers of the lung, colon, brain, ovary, breast, prostate, and kidney. These cell lines were selected partly on pragmatic terms: those selected behaved best under assay conditions. The screen was designed so that for each compound tested, both the absolute and the relative sensitivities of individual cell lines were reproducible to the extent that a characteristic profile or fingerprint of cellular response was generated.

Although the particular inhibitory response of a single cell line might be relatively uninformative, the pattern of response of the cell lines as a group can be used to rank a compound according to the likelihood of sharing common mechanisms. The COMPARE algorithm qualifies this pattern and searches an inventory of screened agents to compile a list of the compounds that have the most similar patterns of cellular sensitivity and resistance.

In 1985, the hypothesis was put forward that the human tumor cell line screen could discover celltype–specific agents with clinical activity against solid tumors. The emerging reality is that correlation of in vitro histology to clinical activity is poor, but the pattern of cellular sensitivity and resistance of the cell lines to the drug correlates with molecular target expression. The screen is now used as a cytotoxic assay but also to identify compounds with activity against cells that may relate to a particular molecular target profile.