commercially available anticancer drugs (Mayfield, 2011). A plated set of about 100 FDA-approved oncology drugs is now available without charge to the research community. Information about this resource and how to obtain it can be found on the Division of Cancer Treatment and Diagnosis Developmental Therapeutics Program website.1

Preclinical Models for Combinations

To assess the effects of combining anticancer agents on tumor growth inhibition, NCI’s toxicogenomics program is testing 5,000 unique combinations for the 100 commercially available anticancer drugs across many clinically relevant concentrations on the NCI-60 panel, which includes 60 human tumor cell lines.

For about 10 percent of the combinations, some synergistic effects appear to be greater than the additive effects alone. The researchers are trying to confirm synergistic activity in a variety of different xenograft animal models. Some of the antagonistic or additive effects that have been observed were unpredicted, Dr. Doroshow noted. For example, some cell lines that are insensitive to the individual agents used in the combination, such as dasatinib and 6-MP, are sensitive when the agents are used in combination. “This shows us that there are many things about the drugs, old and new, that we think we know and, in fact, we don’t,” Dr. Doroshow said. “Such systematic screening will provide, we hope, novel information for the investigative community to help us understand how to put some of these agents together.”

Dr. Doroshow estimated that all 5,000 combinations will be evaluated by the end of 2011, at which time the data will be made publicly available on the NCI website. NCI scientists are also modeling the effectiveness of combining investigational agents with approved agents. Furthermore, they are exploring combinations of 300 investigational agents in a variety of concentrations (Mayfield, 2011). Dr. Blackman suggested researchers correlate the findings from NCI’s combination screening program to clinical data on such combinations to assess how predictive the assays are. Dr. Doroshow responded that it certainly can be done across the NCI database of Phase II trials. Dr. Amy Abernethy, director of the Duke Cancer Care Research Program, suggested testing combinations of oncology and non-oncology commercially available drugs for their antitumor effects, and Dr. Doroshow responded, “Repurposing non-oncologic drugs is not something we are doing, but is something of significant interest to Dr.

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1 See http://dtp.nci.nih.gov/branches/dscb/oncology_drugset_explanation.html (accessed December 14, 2011).



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