{"doi":"10.1016/j.bbcan.2025.189413","title":"Histological transformation in lung cancer: Mechanisms, clinical characteristics, and therapeutic approaches","abstract":null,"journal":"Biochimica et Biophysica Acta (BBA) - Reviews on Cancer","year":2025,"id":631365,"datarank":0.3958585994422889,"base_score":2.639057329615259,"endowment":2.639057329615259,"self_citation_contribution":0.3958585994422889,"citation_network_contribution":0.0,"self_endowment_contribution":0.3958585994422889,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":13,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1319499,"name":"Tao Xu","orcid":"0000-0003-2234-7737","position":1,"is_corresponding":false},{"id":1636135,"name":"Xiaojing Cao","orcid":null,"position":2,"is_corresponding":false},{"id":227659,"name":"Hecheng Li","orcid":"0000-0001-8069-6033","position":3,"is_corresponding":false},{"id":1636136,"name":"Runsen Jin","orcid":null,"position":4,"is_corresponding":false},{"id":44477,"name":"Shiyi Liu","orcid":"0000-0001-6139-8380","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Histological transformation in lung cancer: Mechanisms, clinical characteristics, and therapeutic approaches","abstract":"Lung cancer, the leading cause of cancer-related mortality globally, exhibits remarkable histological plasticity, with non-small cell lung cancer (NSCLC) frequently transforming into small cell lung cancer (SCLC) as a resistance mechanism to targeted therapies and immunotherapies. The molecular mechanisms and treatments for SCLC transformation remain unclear. This review analyzes the mechanisms, molecular features, and treatment landscape of histological transformation, particularly in EGFR-mutant NSCLC. Key findings include: (1) RB1 and TP53 co-inactivation is a hallmark of transformed SCLC, enabling lineage plasticity via epigenetic and neuroendocrine changes; (2) the tumor immune microenvironment becomes immunosuppressive during transformation; and (3) new therapies targeting DLL3 and AURKA show promise in early trials. This study offers a comprehensive framework to understand histological transformation in lung cancer. It underscores the importance of routine re-biopsies for early detection and supports the development of biomarker-guided therapies. Future research should validate predictive biomarkers and optimizing combination therapies for transformed SCLC.","is_dataset_classified":null,"base_score":2.4849066497880004,"endowment":2.4849066497880004,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"40784437","pmcid":null,"openalex_id":"https://openalex.org/W4413101264","authors":[],"funders":[{"funder_name":"Natural Science Foundation of Shanghai Municipality","grant_id":"22ZR1439200","title":null},{"funder_name":"National Natural Science Foundation of China","grant_id":"82372855","title":null},{"funder_name":"National Natural Science Foundation of China","grant_id":"82072557","title":null},{"funder_name":"Shanghai Jiao Tong University","grant_id":"YG2023ZD04","title":null},{"funder_name":"National Key Research and Development Program of China","grant_id":"2021YFC2500900","title":null},{"funder_name":"Shanghai Municipal Health Commission","grant_id":"2022JC023","title":null}],"total_grants":6,"fwci":5.3392,"citation_percentile":0.96672534,"influential_citations":0,"citation_trend":[{"year":2026,"count":11}],"oa_status":"hybrid","license":"cc-by","oa_locations":[{"url":"https://doi.org/10.1016/j.bbcan.2025.189413","host_type":"journal"},{"url":"https://doi.org/10.1016/j.bbcan.2025.189413","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S0304419X25001556?httpAccept=text/xml","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S0304419X25001556?httpAccept=text/plain","host_type":"publisher"},{"url":"https://pubmed.ncbi.nlm.nih.gov/40784437","host_type":"repository"}],"fields_of_study":["Lung Cancer Research Studies","Lung Cancer Treatments and Mutations","Cancer Genomics and Diagnostics","Humans","Lung Neoplasms","Tumor Microenvironment","Cell Transformation, Neoplastic","Small Cell Lung Carcinoma","Carcinoma, Non-Small-Cell Lung","Biomarkers, Tumor","Tumor Suppressor Protein p53","Retinoblastoma Binding Proteins","Mutation","Molecular Targeted Therapy","Membrane Proteins","Ubiquitin-Protein Ligases","Intracellular Signaling Peptides and Proteins"],"mesh_terms":["Carcinoma, Non-Small-Cell Lung","Cell Transformation, Neoplastic","Humans","Lung Neoplasms","Membrane Proteins","Mutation","Biomarkers, Tumor","Tumor Suppressor Protein p53","Ubiquitin-Protein Ligases","Intracellular Signaling Peptides and Proteins","Small Cell Lung Carcinoma","Retinoblastoma Binding Proteins","Molecular Targeted Therapy","Tumor Microenvironment"],"keywords":["Lung cancer","Biomarker","Immunotherapy","Epigenetics","Cancer research","Medicine","Cancer","Clinical trial","Targeted therapy","Malignant transformation","Mechanism (biology)","Oncology","Biology","Pathology","Internal medicine","Gene","NSCLC","Tumor Microenvironment","SCLC","Histological Transformation","Lineage Plasticity"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-05T23:25:58.852144Z","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":[]}