The National Cancer Institute ALMANAC: A Comprehensive Screening Resource for the Detection of Anticancer Drug Pairs with Enhanced Therapeutic Activity
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 re...
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| Veröffentlicht in: | Cancer research (Chicago, Ill.) Ill.), 2017-07, Vol.77 (13), p.3564-3576 |
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| creator | Holbeck, Susan L Camalier, Richard Crowell, James A Govindharajulu, Jeevan Prasaad Hollingshead, Melinda Anderson, Lawrence W Polley, Eric Rubinstein, Larry Srivastava, Apurva Wilsker, Deborah Collins, Jerry M Doroshow, James H |
| description | 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
experiments in mouse xenograft models of human cancer confirmed combinations with greater than single-agent efficacy. Concomitant detection of mechanistic biomarkers for these combinations
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.
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| doi_str_mv | 10.1158/0008-5472.CAN-17-0489 |
| format | Article |
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experiments in mouse xenograft models of human cancer confirmed combinations with greater than single-agent efficacy. Concomitant detection of mechanistic biomarkers for these combinations
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.
.</description><identifier>ISSN: 0008-5472</identifier><identifier>ISSN: 1538-7445</identifier><identifier>EISSN: 1538-7445</identifier><identifier>DOI: 10.1158/0008-5472.CAN-17-0489</identifier><identifier>PMID: 28446463</identifier><language>eng</language><publisher>United States: American Association for Cancer Research, Inc</publisher><subject>Animal models ; Animals ; Antineoplastic Combined Chemotherapy Protocols - pharmacology ; Antitumor activity ; Bortezomib ; Cancer ; Cell Line, Tumor ; Clinical trials ; Drug resistance ; Drug Screening Assays, Antitumor ; Drugs ; Humans ; Mice ; National Cancer Institute (U.S.) ; Paclitaxel ; Small Molecule Libraries - pharmacology ; Subpopulations ; Translation ; Tumor cell lines ; Tumors ; United States ; Xenograft Model Antitumor Assays ; Xenografts</subject><ispartof>Cancer research (Chicago, Ill.), 2017-07, Vol.77 (13), p.3564-3576</ispartof><rights>2017 American Association for Cancer Research.</rights><rights>Copyright American Association for Cancer Research, Inc. Jul 1, 2017</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c524t-dd9c6dfa88fe8edd951d3d583498ab4c9f459fcfd9fec3ae7d269c8ae9f01bb43</citedby><cites>FETCH-LOGICAL-c524t-dd9c6dfa88fe8edd951d3d583498ab4c9f459fcfd9fec3ae7d269c8ae9f01bb43</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,777,781,882,3343,27905,27906</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28446463$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Holbeck, Susan L</creatorcontrib><creatorcontrib>Camalier, Richard</creatorcontrib><creatorcontrib>Crowell, James A</creatorcontrib><creatorcontrib>Govindharajulu, Jeevan Prasaad</creatorcontrib><creatorcontrib>Hollingshead, Melinda</creatorcontrib><creatorcontrib>Anderson, Lawrence W</creatorcontrib><creatorcontrib>Polley, Eric</creatorcontrib><creatorcontrib>Rubinstein, Larry</creatorcontrib><creatorcontrib>Srivastava, Apurva</creatorcontrib><creatorcontrib>Wilsker, Deborah</creatorcontrib><creatorcontrib>Collins, Jerry M</creatorcontrib><creatorcontrib>Doroshow, James H</creatorcontrib><title>The National Cancer Institute ALMANAC: A Comprehensive Screening Resource for the Detection of Anticancer Drug Pairs with Enhanced Therapeutic Activity</title><title>Cancer research (Chicago, Ill.)</title><addtitle>Cancer Res</addtitle><description>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
experiments in mouse xenograft models of human cancer confirmed combinations with greater than single-agent efficacy. Concomitant detection of mechanistic biomarkers for these combinations
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.
.</description><subject>Animal models</subject><subject>Animals</subject><subject>Antineoplastic Combined Chemotherapy Protocols - pharmacology</subject><subject>Antitumor activity</subject><subject>Bortezomib</subject><subject>Cancer</subject><subject>Cell Line, Tumor</subject><subject>Clinical trials</subject><subject>Drug resistance</subject><subject>Drug Screening Assays, Antitumor</subject><subject>Drugs</subject><subject>Humans</subject><subject>Mice</subject><subject>National Cancer Institute (U.S.)</subject><subject>Paclitaxel</subject><subject>Small Molecule Libraries - pharmacology</subject><subject>Subpopulations</subject><subject>Translation</subject><subject>Tumor cell lines</subject><subject>Tumors</subject><subject>United States</subject><subject>Xenograft Model Antitumor Assays</subject><subject>Xenografts</subject><issn>0008-5472</issn><issn>1538-7445</issn><issn>1538-7445</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFksGO0zAQhi0EYsvCI4AsceGSxU7sxOaAFGUXWKkUBMvZcp1x41XrFNsp2ifhdXHUpQIu-GKN5vt_jcc_Qs8puaCUi9eEEFFw1pQXXbsqaFMQJuQDtKC8EkXDGH-IFifmDD2J8TaXnBL-GJ2VgrGa1dUC_bwZAK90cqPXW9xpbyDgax-TS1MC3C4_tqu2e4Nb3I27fYABfHQHwF9NAPDOb_AXiOMUDGA7Bpyy2yUkMLMhHi1ufXLm6HoZpg3-rF2I-IdLA77yw9zocR4h6D1MmcRtVh5cunuKHlm9jfDs_j5H395d3XQfiuWn99dduywML1kq-l6aurdaCAsCcsVpX_VcVEwKvWZGWsalNbaXFkyloenLWhqhQVpC12tWnaO3R9_9tN5Bb8CnoLdqH9xOhzs1aqf-7ng3qM14UJzJfOps8OreIIzfJ4hJ7Vw0sN1qD-MUFZVUSp4X3vwfFbJsyqopeUZf_oPe5iXnL5oNRVVyIjnJFD9SJowxBrCnuSlRc0rUnAA1J0DllCjaqDklWffiz0efVL9jUf0C-IW7qw</recordid><startdate>20170701</startdate><enddate>20170701</enddate><creator>Holbeck, Susan L</creator><creator>Camalier, Richard</creator><creator>Crowell, James A</creator><creator>Govindharajulu, Jeevan Prasaad</creator><creator>Hollingshead, Melinda</creator><creator>Anderson, Lawrence W</creator><creator>Polley, Eric</creator><creator>Rubinstein, Larry</creator><creator>Srivastava, Apurva</creator><creator>Wilsker, Deborah</creator><creator>Collins, Jerry M</creator><creator>Doroshow, James H</creator><general>American Association for Cancer Research, Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7T5</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>7QO</scope><scope>5PM</scope></search><sort><creationdate>20170701</creationdate><title>The National Cancer Institute ALMANAC: A Comprehensive Screening Resource for the Detection of Anticancer Drug Pairs with Enhanced Therapeutic Activity</title><author>Holbeck, Susan L ; 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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
experiments in mouse xenograft models of human cancer confirmed combinations with greater than single-agent efficacy. Concomitant detection of mechanistic biomarkers for these combinations
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.
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| ispartof | Cancer research (Chicago, Ill.), 2017-07, Vol.77 (13), p.3564-3576 |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; American Association for Cancer Research |
| subjects | Animal models Animals Antineoplastic Combined Chemotherapy Protocols - pharmacology Antitumor activity Bortezomib Cancer Cell Line, Tumor Clinical trials Drug resistance Drug Screening Assays, Antitumor Drugs Humans Mice National Cancer Institute (U.S.) Paclitaxel Small Molecule Libraries - pharmacology Subpopulations Translation Tumor cell lines Tumors United States Xenograft Model Antitumor Assays Xenografts |
| title | The National Cancer Institute ALMANAC: A Comprehensive Screening Resource for the Detection of Anticancer Drug Pairs with Enhanced Therapeutic Activity |
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