The National Cancer Institute ALMANAC: A comprehensive screening resource for the detection of anticancer drug pairs with enhanced therapeutic activity

Susan L. Holbeck, Richard Camalier, James A. Crowell, Jeevan Prasaad Govindharajulu, Melinda Hollingshead, Lawrence W. Anderson, Eric Polley, Larry Rubinstein, Apurva Srivastava, Deborah Wilsker, Jerry M. Collins, James H. Doroshow

Research output: Contribution to journalArticlepeer-review

67 Scopus citations

Abstract

To date, over 100 small-molecule oncology drugs have been approved by the FDA. Because of the inherent heterogeneity of tumors, these small molecules are often administered in combination to prevent emergence of resistant cell subpopulations. Therefore, new combination strategies to overcome drug resistance in patients with advanced cancer are needed. In this study, we performed a systematic evaluation of the therapeutic activity of over 5,000 pairs of FDA-approved cancer drugs against a panel of 60 well-characterized human tumor cell lines (NCI-60) to uncover combinations with greater than additive growth-inhibitory activity. Screening results were compiled into a database, termed the NCI-ALMANAC (A Large Matrix of Anti-Neoplastic Agent Combinations), publicly available at https://dtp.cancer.gov/ncial manac. Subsequent in vivo experiments in mouse xenograft models of human cancer confirmed combinations with greater than single-agent efficacy. Concomitant detection of mechanistic biomarkers for these combinations in vivo supported the initiation of two phase I clinical trials at the NCI to evaluate clofarabine with bortezomib and nilotinib with paclitaxel in patients with advanced cancer. Consequently, the hypothesis-generating NCI-ALMANAC web-based resource has demonstrated value in identifying promising combinations of approved drugs with potent anticancer activity for further mechanistic study and translation to clinical trials.

Original languageEnglish (US)
Pages (from-to)3564-3576
Number of pages13
JournalCancer research
Volume77
Issue number13
DOIs
StatePublished - Jul 1 2017

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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