Related Experiment Video
Updated: Mar 3, 2026
Author Spotlight: Exploring the Role of Ion Channels in Cancer: Characterization and Potential Treatment Approaches
Published on: June 16, 2023
The National Cancer Institute ALMANAC: A Comprehensive Screening Resource for the Detection of Anticancer Drug Pairs
Susan L Holbeck1, Richard Camalier1, James A Crowell1
1Division of Cancer Treatment and Diagnosis, National Cancer Institute, NIH, Bethesda, Maryland.
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/ncialmanac 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. Cancer Res; 77(13); 3564-76. ©2017 AACR.
Insights
Researchers screened over 5,000 FDA-approved cancer drug pairs to find effective combinations for overcoming tumor resistance. This led to the NCI-ALMANAC database and two new clinical trials for advanced cancer treatments.
Area of Science:
- Oncology
- Pharmacology
- Bioinformatics
Background:
- Over 100 small-molecule oncology drugs are FDA-approved.
- Tumor heterogeneity necessitates combination drug strategies to prevent resistance.
- New approaches are needed to overcome drug resistance in advanced cancers.
Purpose of the Study:
- To systematically evaluate over 5,000 FDA-approved cancer drug pairs for synergistic anticancer activity.
- To identify novel drug combinations that exhibit greater than additive growth-inhibitory effects.
- To create a publicly available database (NCI-ALMANAC) of these drug combinations.
Main Methods:
- Screening of over 5,000 drug pairs against the NCI-60 human tumor cell line panel.
- Compilation of screening results into the NCI-ALMANAC database.
- In vivo validation in mouse xenograft models and biomarker detection.
Main Results:
- Identification of numerous drug combinations with greater than single-agent efficacy.
- Confirmation of synergistic activity in preclinical models.
- Initiation of two Phase I clinical trials based on promising combinations (clofarabine with bortezomib, nilotinib with paclitaxel).
Conclusions:
- The NCI-ALMANAC resource effectively identifies promising drug combinations for cancer therapy.
- Systematic screening of approved drugs can accelerate the discovery of new combination strategies.
- Validated combinations show potential for clinical translation in advanced cancer patients.
