In an effort to find novel drug combinations that are more effective than single agents, scientists in the United States have tested all possible pairings of the 100 cancer drugs currently approved for patients.

Susan Holbeck, PhD, a biologist in the division of cancer treatment and diagnosis at the NCI, told audience members at the American Association for Cancer Research (AACR)-NCI-European Organization for Research and Treatment of Cancer (EORTC) International Conference on Molecular Targets and Cancer Therapeutics held last November in Dublin, Ireland, that she and her colleagues had completed their testing of 5000 combinations of the 100 cancer drugs. Their work included 300,000 experiments to test the combinations in 60 cell lines developed by the NCI. Because the drugs are all approved, they can potentially be translated rapidly into the clinic, she said.

Dr. Holbeck added that a large number of the combinations have never been used in people and have no experimental information available. She and her colleagues decided to test all possible combinations of pairs and make the data publicly available to support additional experiments that could lead to new combinations reaching clinical trials. Not only did they test “rational” combinations, which some groups have done by making scientific inferences about which pathways would make sense to block simultaneously with different drugs, but they also were able to test drug pairs that would not otherwise be tested together.

Their work was accomplished by using human tumor cell lines derived from 9 different types of cancer. This NCI-60 panel has been used to screen potential new drugs for many years. Because mutations, gene expression, microRNA expression, and other attributes have already been characterized, scientists can analyze the cell lines that benefit from certain combinations and identify potential biomarkers.

When some of the new combinations were tested in human tumors grafted into mice, they were found to be more effective than most active doses of single drugs. Researchers will need to repeat and confirm the results but hope to rapidly translate some of the new combinations into clinical trials. The data still must be published, but it will eventually be made available on the NCI's Web site for all to use, according to Dr. Holbeck.