{"doi":"10.1016/j.canlet.2025.217759","title":"Sonrotoclax (BGB-11417) synergistically amplifies the radiotherapy-elicited anti-tumor immune response","abstract":null,"journal":"Cancer Letters","year":2025,"id":619582,"datarank":0.3596842909197557,"base_score":2.3978952727983707,"endowment":2.3978952727983707,"self_citation_contribution":0.3596842909197557,"citation_network_contribution":0.0,"self_endowment_contribution":0.3596842909197557,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":10,"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":1599009,"name":"Zengfu Zhang","orcid":null,"position":1,"is_corresponding":false},{"id":277413,"name":"Chen Tian","orcid":"0000-0002-0995-990X","position":2,"is_corresponding":false},{"id":366621,"name":"Xu Liu","orcid":"0000-0003-2252-7148","position":3,"is_corresponding":false},{"id":267942,"name":"Meng Wu","orcid":"0000-0002-8533-6886","position":4,"is_corresponding":false},{"id":376804,"name":"Jinming Yu","orcid":"0009-0006-5449-2356","position":5,"is_corresponding":false},{"id":1599014,"name":"Jupeng Yuan","orcid":"0000-0003-1817-7771","position":6,"is_corresponding":false},{"id":236009,"name":"Dawei Chen","orcid":"0000-0002-6762-7997","position":7,"is_corresponding":false},{"id":1599008,"name":"Mengmeng Ma","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Sonrotoclax (BGB-11417) synergistically amplifies the radiotherapy-elicited anti-tumor immune response","abstract":"Escape from apoptosis is one of the main hallmarks of cancer. The imbalance of BCL-2 family members is a key factor leading to radiotherapy resistance. Targeting BCL-2 can overcome radiotherapy resistance by promoting apoptosis. Nevertheless, the function of BCL-2 in regulating the tumor immune microenvironment (TIME) is still not well understood. Herein, we discovered that the specific BCL-2 inhibitor sonrotoclax (BGB-11417) boosted the effectiveness of radiotherapy in an immune-mediated manner. Using flow cytometry, we found that sonrotoclax combined with radiotherapy polarized tumor-associated macrophages (TAMs) toward the M1-type and promoted the infiltration of Gzmb<sup>+</sup> CD8<sup>+</sup> T cells into the tumor. Mechanistically, we demonstrated that the combination of sonrotoclax and radiotherapy induced immunogenic ferroptosis of cancer cells by inhibiting GPX4 expression, released tumor-associated damage-associated molecular patterns (DAMPs) and subsequently activated the NF-κB pathway in TAMs. Moreover, the combination therapy also led to aberrant cytosolic DNA abundance and activated the cGAS-STING pathway in cancer cells, leading to the release of type I interferons and enhanced activation of CD8<sup>+</sup> T cells. Meanwhile, the activation of cGAS-STING pathway also led to the upregulation of PD-L1 expression. Further combination of sonrotoclax and radiotherapy plus anti-PD-L1 exerted the most significant anti-tumor effects. Overall, our study indicated that sonrotoclax enhanced the anti-tumor immune response of radiotherapy through non-apoptotic roles of BCL-2, and shed light on the further clinical evaluation of the triple combination therapy of sonrotoclax, radiotherapy and immunotherapy.","is_dataset_classified":null,"base_score":2.302585092994046,"endowment":2.302585092994046,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"40311913","pmcid":null,"openalex_id":"https://openalex.org/W4409907405","authors":[],"funders":[{"funder_name":"Natural Science Foundation of Shandong Province","grant_id":"2024ZD0519902","title":null},{"funder_name":"Natural Science Foundation of Shandong Province","grant_id":"ZR2023MH012","title":null},{"funder_name":"Natural Science Foundation of Shandong Province","grant_id":"ZR2022LZL007","title":null},{"funder_name":"Natural Science Foundation of Shandong Province","grant_id":"ZR2023ZD26","title":null},{"funder_name":"National Natural Science Foundation of China","grant_id":"82172676","title":null},{"funder_name":"National Natural Science Foundation of China","grant_id":"82030082","title":null},{"funder_name":"National Natural Science Foundation of China","grant_id":"82373217","title":null},{"funder_name":"National Natural Science Foundation of China","grant_id":"82373217,82030082","title":null}],"total_grants":8,"fwci":6.5423,"citation_percentile":0.97637985,"influential_citations":0,"citation_trend":[{"year":2025,"count":5},{"year":2026,"count":4}],"oa_status":"closed","license":"https://doi.org/10.15223/policy-004","oa_locations":[{"url":"https://api.elsevier.com/content/article/PII:S0304383525003258?httpAccept=text/xml","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S0304383525003258?httpAccept=text/plain","host_type":"publisher"},{"url":"https://doi.org/10.1016/j.canlet.2025.217759","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/40311913","host_type":"repository"}],"fields_of_study":["Bioactive Compounds and Antitumor Agents","Cancer therapeutics and mechanisms","Pharmacological Receptor Mechanisms and Effects"],"mesh_terms":["Ferroptosis","Tumor-Associated Macrophages","Animals","Female","Humans","Neoplasms","Signal Transduction","Apoptosis","CD8-Positive T-Lymphocytes","Proto-Oncogene Proteins c-bcl-2","Xenograft Model Antitumor Assays","Cell Line, Tumor","Mice","Tumor Microenvironment"],"keywords":["Immune system","Radiation therapy","Cancer research","Medicine","Immunology","Internal medicine","Macrophage","Radiotherapy","Bcl-2 Inhibitor","Cgas-sting","Immunogenic Ferroptosis","Sonrotoclax"],"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":"2026-08-03T07:40:27.160229Z","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":[]}