{"doi":"10.1016/j.canlet.2025.218087","title":"Celebrating the 40-year milestone: NF-ĸB in oncoimmunity","abstract":"Since its discovery by Dr. David Baltimore nearly 40 years ago, and in light of his recent passing, NF-κB has once again come into sharp focus as a central regulator of diverse cellular processes, including immune responses, inflammation, and cell survival. Its dysregulation is implicated in a wide range of human diseases, with mounting evidence highlighting its pivotal role in cancer and oncoimmunity. This review provides an integrated overview of NF-κB family members and their canonical and noncanonical signaling pathways, emphasizing how context-dependent activation orchestrates complex cellular outcomes. Within the tumor microenvironment (TME), NF-κB regulates crosstalk among cancer cells, immune subsets, and stromal components, promoting proliferation, metastasis, and immune evasion. We summarize FDA-approved and orphan-designated drugs targeting NF-κB, along with emerging therapeutics in clinical and preclinical development. Innovative strategies, including tumor-targeted delivery, immune checkpoint combination, nanocatalytic, and epigenetic modulation, are redefining NF-κB-directed therapy. Looking ahead, future efforts should focus on understanding context-specific NF-κB signaling, optimizing combination therapies, improving drug delivery and bioavailability, and identifying predictive biomarkers for patient stratification. Moreover, the emerging integration of artificial intelligence holds promise to accelerate discovery and personalize NF-κB-targeted therapies. Collectively, FDA-approved agents, experimental compounds, and novel strategies underscore NF-κB modulation as a versatile and promising avenue for cancer and immune disease therapy.","journal":"Cancer Letters","year":2025,"id":522237,"datarank":0.26876392038420827,"base_score":1.791759469228055,"endowment":1.791759469228055,"self_citation_contribution":0.26876392038420827,"citation_network_contribution":0.0,"self_endowment_contribution":0.26876392038420827,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":5,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9468,"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":292117,"name":"Tao Lu","orcid":"0000-0002-0013-4987","position":1,"is_corresponding":false},{"id":1074986,"name":"Faranak Alipourgivi","orcid":"0000-0003-2583-8953","position":0,"is_corresponding":true}],"reference_count":119,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:49:54.058858Z","pmid":"41106769","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":[]}