{"doi":"10.3390/cancers12020280","title":"Targeting NRF2-Governed Glutathione Synthesis for SDHB-Mutated Pheochromocytoma and Paraganglioma","abstract":"Succinate dehydrogenase subunit B (SDHB) deficiency frequently occurs in cluster I pheochromocytomas and paragangliomas (PCPGs). SDHB-mutated PCPGs are characterized by alterations in the electron transport chain, metabolic reprogramming of the tricarboxylic cycle, and elevated levels of reactive oxygen species (ROS). We discovered that SDHB-deficient PCPG cells exhibit increased oxidative stress burden, which leads to elevated demands for glutathione metabolism. Mechanistically, nuclear factor erythroid 2-related factor 2 (NRF2)-guided glutathione de novo synthesis plays a key role in supporting cellular survival and the proliferation of SDHB-knockdown (SDHBKD) cells. NRF2 blockade not only disrupted ROS homeostasis in SDHB-deficient cells but also caused severe cytotoxicity by the accumulation of DNA oxidative damage. Brusatol, a potent NRF2 inhibitor, showed a promising effect in suppressing SDHBKD metastatic lesions in vivo, with prolonged overall survival in mice bearing PCPG allografts. Our findings highlight a novel therapeutic strategy of targeting the NRF2-driven glutathione metabolic pathway against SDHB-mutated PCPG.","journal":"Cancers","year":2020,"id":63551,"datarank":1.1130627730600189,"base_score":3.784189633918261,"endowment":3.784189633918261,"self_citation_contribution":0.5676284450877392,"citation_network_contribution":0.5454343279722795,"self_endowment_contribution":0.5676284450877392,"citer_contribution":0.5454343279722795,"corpus_percentile":null,"corpus_rank":null,"citation_count":43,"citer_count":26,"citers_with_citation_signal":20,"citers_with_endowment":20,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9555,"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":336429,"name":"Ying Pang","orcid":"0000-0001-6195-2150","position":1,"is_corresponding":false},{"id":336430,"name":"Veronika Caisová","orcid":"0000-0002-8089-7158","position":2,"is_corresponding":false},{"id":109753,"name":"Jianyi Ding","orcid":"0000-0002-8086-9034","position":3,"is_corresponding":false},{"id":336431,"name":"Di Yu","orcid":"0000-0003-0801-1225","position":4,"is_corresponding":false},{"id":336432,"name":"Yiqiang Zhou","orcid":"0000-0001-8706-9139","position":5,"is_corresponding":false},{"id":338177,"name":"Thanh‐Truc Huynh","orcid":null,"position":6,"is_corresponding":false},{"id":336433,"name":"Hans K. Ghayee","orcid":"0000-0001-9201-3033","position":7,"is_corresponding":false},{"id":70229,"name":"Karel Pacák","orcid":"0000-0002-3541-3767","position":8,"is_corresponding":false},{"id":109756,"name":"Chunzhang Yang","orcid":"0000-0001-6433-0867","position":9,"is_corresponding":false},{"id":275952,"name":"Yang Liu","orcid":"0000-0002-5694-8760","position":0,"is_corresponding":true}],"reference_count":47,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T21:11:24.000992Z","pmid":"31979226","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":[]}