{"doi":"10.1101/2020.05.12.088971","title":"Exploiting KRAS-driven Ferroaddiction in Cancer Through Ferrous Iron-Activatable Drug Conjugates (FeADC)","abstract":"Abstract KRAS mutations cause a quarter of cancer mortality and most are undruggable. Several inhibitors of the MAPK pathway are FDA approved but poorly tolerated at dosages required to adequately extinguish RAS/RAF/MAPK signaling. We found that oncogenic KRAS signaling induces ferrous iron (Fe 2+ ) accumulation early in and throughout KRAS-mediated transformation. We used an FDA-approved MEK inhibitor to produce a prototypical Ferrous Iron–Activatable Drug Conjugate (FeADC) which achieved potent MAPK blockade in tumor cells while sparing normal tissues. This innovation allowed sustainable, effective treatment of tumor bearing animals, with tumor-selective drug activation producing superior systemic tolerability. Ferrous iron accumulation is an exploitable feature of KRAS transformation and FeADCs hold promise for improving treatment of KRAS-driven solid tumors.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":124880,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9534,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":557218,"name":"Ryan K. Muir","orcid":"0000-0001-7041-8996","position":1,"is_corresponding":false},{"id":570122,"name":"Ryan L. Gonciarz","orcid":"0000-0002-6600-7032","position":2,"is_corresponding":false},{"id":1897,"name":"Adam B. Olshen","orcid":"0000-0002-8998-4514","position":3,"is_corresponding":false},{"id":264380,"name":"Iwei Yeh","orcid":"0000-0002-3941-3561","position":4,"is_corresponding":false},{"id":323013,"name":"Byron Hann","orcid":"0000-0002-0715-5166","position":5,"is_corresponding":false},{"id":465296,"name":"Ning Zhao","orcid":"0000-0003-3699-3369","position":6,"is_corresponding":false},{"id":466439,"name":"Yung-Hua Wang","orcid":null,"position":7,"is_corresponding":false},{"id":272318,"name":"Spencer C. Behr","orcid":"0000-0001-9400-0543","position":8,"is_corresponding":false},{"id":1892,"name":"James E. Korkola","orcid":null,"position":9,"is_corresponding":false},{"id":465302,"name":"Michael J. Evans","orcid":"0000-0003-4947-1316","position":10,"is_corresponding":false},{"id":20519,"name":"Eric A. Collisson","orcid":"0000-0001-8037-9388","position":11,"is_corresponding":false},{"id":490827,"name":"Adam R. Renslo","orcid":"0000-0002-1240-2846","position":12,"is_corresponding":false},{"id":264054,"name":"Honglin Jiang","orcid":"0000-0001-5193-6309","position":0,"is_corresponding":true}],"reference_count":63,"raw_metadata":null,"created_at":"2026-07-18T23:15:11.632153Z","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":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}