{"doi":"10.3389/fonc.2022.946320","title":"Redox integration of signaling and metabolism in a head and neck cancer model of radiation resistance using COSMRO","abstract":"Redox metabolism is increasingly investigated in cancer as driving regulator of tumor progression, response to therapies and long-term patients’ quality of life. Well-established cancer therapies, such as radiotherapy, either directly impact redox metabolism or have redox-dependent mechanisms of action defining their clinical efficacy. However, the ability to integrate redox information across signaling and metabolic networks to facilitate discovery and broader investigation of redox-regulated pathways in cancer remains a key unmet need limiting the advancement of new cancer therapies. To overcome this challenge, we developed a new constraint-based computational method (COSM ro ) and applied it to a Head and Neck Squamous Cell Cancer (HNSCC) model of radiation resistance. This novel integrative approach identified enhanced capacity for H 2 S production in radiation resistant cells and extracted a key relationship between intracellular redox state and cholesterol metabolism; experimental validation of this relationship highlights the importance of redox state in cellular metabolism and response to radiation.","journal":"Frontiers in Oncology","year":2023,"id":365075,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9464,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":712072,"name":"Jade Moore","orcid":"0000-0001-8092-3363","position":1,"is_corresponding":false},{"id":1121056,"name":"Nelmi O. Devarie‐Baez","orcid":null,"position":2,"is_corresponding":false},{"id":373946,"name":"Joshua E. Lewis","orcid":"0000-0002-4168-0407","position":3,"is_corresponding":false},{"id":537503,"name":"Hanzhi Wu","orcid":"0000-0001-7822-4432","position":4,"is_corresponding":false},{"id":428144,"name":"Kirtikar Shukla","orcid":"0000-0002-1789-4990","position":5,"is_corresponding":false},{"id":1121057,"name":"Elsa I. Silva Lopez","orcid":null,"position":6,"is_corresponding":false},{"id":350208,"name":"Victor Vitvitsky","orcid":"0000-0001-6251-6115","position":7,"is_corresponding":false},{"id":641375,"name":"Chia-Chi Chuang Key","orcid":null,"position":8,"is_corresponding":false},{"id":673692,"name":"Mercedes Porosnicu","orcid":"0000-0003-3651-8867","position":9,"is_corresponding":false},{"id":373952,"name":"Melissa L. Kemp","orcid":"0000-0003-3781-8802","position":10,"is_corresponding":false},{"id":265994,"name":"Ruma Banerjee","orcid":"0000-0001-8332-3275","position":11,"is_corresponding":false},{"id":299668,"name":"John S. Parks","orcid":"0000-0002-5227-8915","position":12,"is_corresponding":false},{"id":429246,"name":"Allen W. Tsang","orcid":null,"position":13,"is_corresponding":false},{"id":246826,"name":"Xiaobo Zhou","orcid":"0000-0001-7191-6495","position":14,"is_corresponding":false},{"id":285814,"name":"Cristina M. Furdui","orcid":"0000-0003-3771-7999","position":15,"is_corresponding":false},{"id":1120591,"name":"Zhiwei Ji","orcid":"0000-0001-5781-3465","position":0,"is_corresponding":true}],"reference_count":37,"raw_metadata":null,"created_at":"2026-07-19T01:14:46.760245Z","pmid":"36686772","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":[]}