{"doi":"10.1016/j.coph.2025.102604","title":"Advancements in targeted therapies for acute myeloid leukemia","abstract":"For decades, the only therapeutic option for acute myeloid leukemia (AML) had been intensive combination chemotherapy. In recent years, understanding of the molecular mechanisms underlying myeloid oncogenesis has grown immensely and has led to the development of multiple effective small molecule inhibitors of aberrant cellular signaling. This review highlights the major AML mutational pathways currently being targeted with precision therapies: the receptor tyrosine kinase FLT3, the citric acid cycle enzymes IDH1 and IDH2, and the transcription-regulating KMT2A and NPM1 genes. We review the major clinical trials evaluating the safety and efficacy of agents targeting these pathways, as well as ongoing and upcoming studies of novel and combination therapies for these molecular subsets of AML. • Intensive chemotherapy was historically the only therapeutic option for AML. • Advances in molecular genetics and next-generation sequencing have identified multiple leukemogenic cellular pathways as potential therapeutic targets. • Inhibitors of pro-proliferative FLT3 mutations in AML improve remission induction, survival, and ability to salvage relapses without adding toxicity. • IDH mutations result in maturation arrest, and inhibitors of IDH1 and IDH2 are effective, well-tolerated therapy options for IDH -mutated AML. • Menin inhibitors can block aberrant epigenetic regulatory pathways in KMT2A -rearranged and NPM1 -mutated AML.","journal":"Current Opinion in Pharmacology","year":2025,"id":549804,"datarank":0.10397207708399181,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"self_citation_contribution":0.10397207708399181,"citation_network_contribution":0.0,"self_endowment_contribution":0.10397207708399181,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9498,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1444529,"name":"Adam Barsouk","orcid":"0000-0003-2333-7530","position":1,"is_corresponding":false},{"id":857825,"name":"Omar Elghawy","orcid":"0000-0002-0786-8035","position":2,"is_corresponding":false},{"id":257804,"name":"Catherine Lai","orcid":"0000-0001-8861-0281","position":3,"is_corresponding":false},{"id":1314168,"name":"Matthew P. Connor","orcid":"0000-0003-1186-0623","position":0,"is_corresponding":true}],"reference_count":79,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:54:12.321988Z","pmid":"41576755","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":[]}