{"doi":"10.1038/ncomms16022","title":"Reversal of cancer gene expression correlates with drug efficacy and reveals therapeutic targets","abstract":"The decreasing cost of genomic technologies has enabled the molecular characterization of large-scale clinical disease samples and of molecular changes upon drug treatment in various disease models. Exploring methods to relate diseases to potentially efficacious drugs through various molecular features is critically important in the discovery of new therapeutics. Here we show that the potency of a drug to reverse cancer-associated gene expression changes positively correlates with that drug's efficacy in preclinical models of breast, liver and colon cancers. Using a systems-based approach, we predict four compounds showing high potency to reverse gene expression in liver cancer and validate that all four compounds are effective in five liver cancer cell lines. The in vivo efficacy of pyrvinium pamoate is further confirmed in a subcutaneous xenograft model. In conclusion, this systems-based approach may be complementary to the traditional target-based approach in connecting diseases to potentially efficacious drugs.","journal":"Nature Communications","year":2017,"id":2523,"datarank":0.8208406010507213,"base_score":5.472270673671475,"endowment":5.472270673671475,"self_citation_contribution":0.8208406010507213,"citation_network_contribution":0.0,"self_endowment_contribution":0.8208406010507213,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":237,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.0477,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2017-07-12","fair_score":80.0,"fair_percentile":99.49428320140721,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":18150,"name":"Li Ma","orcid":"0000-0002-9208-1711","position":1,"is_corresponding":false},{"id":15913,"name":"Hyojung Paik","orcid":null,"position":2,"is_corresponding":false},{"id":2824,"name":"Marina Sirota","orcid":"0000-0002-7246-6083","position":3,"is_corresponding":false},{"id":18149,"name":"Wei Wei","orcid":"0000-0002-7566-2995","position":4,"is_corresponding":false},{"id":18153,"name":"Mei-Sze Chua","orcid":null,"position":5,"is_corresponding":false},{"id":18154,"name":"Samuel So","orcid":"0000-0003-3108-086X","position":6,"is_corresponding":false},{"id":51,"name":"Atul Janardhan Butte","orcid":"0000-0002-7433-2740","position":7,"is_corresponding":false},{"id":15919,"name":"Harikrishna Paik","orcid":"0000-0002-3994-0695","position":8,"is_corresponding":false},{"id":18155,"name":"Mei‐Sze Chua","orcid":"0000-0002-3282-4894","position":9,"is_corresponding":false},{"id":11850,"name":"BIN CHEN","orcid":"0000-0001-8858-874X","position":0,"is_corresponding":true}],"reference_count":63,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-03-01T18:20:47.508186Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":100.0,"fair_a":70.0,"fair_i":100.0,"fair_r":50.0,"fair_zscore":3.1468,"fair_rationale":{"fair_score":80.0,"has_llm":false,"dimensions":{"F":{"name":"Findable","score":100.0,"criteria":[{"key":"f_has_doi","label":"Has a persistent DOI","kind":"deterministic","weight":1.0,"fraction":1.0,"signal":"DOI present","rationale":null},{"key":"f_repository_presence","label":"Indexed in repositories / literature DBs","kind":"deterministic","weight":1.0,"fraction":1.0,"signal":"datacite=25, pmcid=True, pmid=True","rationale":null},{"key":"f_persistent_ids","label":"Resolvable scholarly identifiers (OpenAlex)","kind":"deterministic","weight":0.5,"fraction":1.0,"signal":"OpenAlex id present","rationale":null}]},"A":{"name":"Accessible","score":70.0,"criteria":[{"key":"a_open_access","label":"Open Access / files deposited","kind":"deterministic","weight":1.5,"fraction":0.5,"signal":"files/OA location present but not flagged OA","rationale":null},{"key":"a_retrievable","label":"Free full text retrievable","kind":"deterministic","weight":1.0,"fraction":1.0,"signal":"16 OA location(s)","rationale":null}]},"I":{"name":"Interoperable","score":100.0,"criteria":[{"key":"i_linked_data","label":"Linked datasets / DataCite relations","kind":"deterministic","weight":1.0,"fraction":1.0,"signal":"linked_datasets=25, datacite=25","rationale":null},{"key":"i_standard_ids","label":"References data via standard accessions","kind":"deterministic","weight":1.0,"fraction":1.0,"signal":"accessions=1, trials=0","rationale":null}]},"R":{"name":"Reusable","score":50.0,"criteria":[{"key":"r_license","label":"Clear, open reuse license","kind":"deterministic","weight":1.5,"fraction":1.0,"signal":"open license (cc-by)","rationale":null},{"key":"r_downloads","label":"Demonstrated reuse (downloads)","kind":"deterministic","weight":0.5,"fraction":0.0,"signal":"downloads=0","rationale":null},{"key":"r_version","label":"Versioned / maintained","kind":"deterministic","weight":0.5,"fraction":0.0,"signal":"no version chain","rationale":null},{"key":"r_dataset","label":"Classified as a data resource","kind":"deterministic","weight":0.5,"fraction":0.0,"signal":"not a dataset","rationale":null}]}},"suggestions":["Maintain explicit versioning for the dataset.","Make the paper/data Open Access or deposit the files in an open repository."],"model":null,"agent_version":"fair_agent_v1","fulltext_source":"epmc_xml"},"fair_model":null,"fair_agent_version":"fair_agent_v1","fair_fulltext_source":"epmc_xml","fair_has_llm":false,"fair_computed_at":"2026-06-10T09:14:34.497222Z","clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}