{"id":"ad59d149-b6c6-5fc5-9337-d0cc6193397a","stable_key":"e3f6ce02-0bd7-5103-acc1-68503ab6751b:cancer-drug-rescue","predicate":"context_dependent_observation","statement":"ALCAR reversed increased sensitivity to DNA-damaging agents caused by disruption of the alpha-ketoglutarate–carnitine axis.","claim_class":"observational","status":"source_recorded","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"b5025dec-6b9d-54da-9652-db3f717c56ab","mechanism_event_label":"ALCAR reversed increased sensitivity to DNA-damaging agents caused by disruption of the alpha-ketoglutarate–carnitine axis.","subject":{"id":"5ce394a9-6ec6-56dd-866f-37d85c0556e4","slug":"acetylcarnitine","display_name":"Acetyl-L-carnitine","entity_type_key":"small_molecule"},"object":{"id":"bde591f9-f239-51be-9a7e-62bd66227719","slug":"human-cancer-alcar-drug-survival","display_name":"Human cancer-cell survival with DNA-damaging treatment","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"b5025dec-6b9d-54da-9652-db3f717c56ab","stable_key":"e3f6ce02-0bd7-5103-acc1-68503ab6751b:cancer-drug-rescue-event","event_type":"experimental_observation","label":"ALCAR reversed increased sensitivity to DNA-damaging agents caused by disruption of the alpha-ketoglutarate–carnitine axis.","description":"### cancer-drug-rescue\n\nALCAR reversed increased sensitivity to DNA-damaging agents caused by disruption of the alpha-ketoglutarate–carnitine axis.\nThe study tested distinct upstream restrictions including IDH1 inhibition, glutamine starvation and TMLHE knockdown. Propionylcarnitine and butyrylcarnitine did not reproduce this rescue. This is a context-qualified summary of rescue contrasts, not an isolated basal ALCAR effect.\nModel and exposure: Human HR-proficient CCNE1 cancer-cell models; Results and supplementary Fig. 3.\nLimitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.\nReference: αKG-mediated carnitine synthesis drives DNA repair via histone acetylation. | 2026 | https://pubmed.ncbi.nlm.nih.gov/42203879/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC13307467/ | https://doi.org/10.1038/s41586-026-10584-7 | Access: Primary full text: relevant Results/Methods and figure descriptions reviewed; supplements only where explicitly stated.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"5ce394a9-6ec6-56dd-866f-37d85c0556e4","slug":"acetylcarnitine","display_name":"Acetyl-L-carnitine","entity_type_key":"small_molecule"},"role":"recorded factor","stoichiometry":null,"state_label":"as reported","sequence_order":0,"notes":""},{"entity":{"id":"bde591f9-f239-51be-9a7e-62bd66227719","slug":"human-cancer-alcar-drug-survival","display_name":"Human cancer-cell survival with DNA-damaging treatment","entity_type_key":"cellular_process"},"role":"measured outcome","stoichiometry":null,"state_label":"mixed","sequence_order":1,"notes":""},{"entity":{"id":"628ddc2d-e4d9-59c7-ae76-0c0cab80a6b1","slug":"2-oxoglutarate","display_name":"2-Oxoglutarate","entity_type_key":"small_molecule"},"role":"upstream cosubstrate","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"8637bb39-2c30-5168-baaf-3e613d831db0","slug":"glutamine","display_name":"L-Glutamine","entity_type_key":"small_molecule"},"role":"upstream nutrient","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"3f888cec-e779-5b46-bd59-e5317d4bf6aa","slug":"tmlhe","display_name":"Trimethyllysine hydroxylase / TMLHE","entity_type_key":"protein"},"role":"upstream synthesis machinery","stoichiometry":null,"state_label":"","sequence_order":4,"notes":""},{"entity":{"id":"e4c89513-41b4-54d5-9dbd-0baee186b26a","slug":"olaparib","display_name":"Olaparib","entity_type_key":"drug"},"role":"tested treatment","stoichiometry":null,"state_label":"","sequence_order":5,"notes":""},{"entity":{"id":"bdb83796-78cf-5b54-9ca6-4dab19b33600","slug":"cisplatin","display_name":"Cisplatin","entity_type_key":"drug"},"role":"tested treatment","stoichiometry":null,"state_label":"","sequence_order":6,"notes":""},{"entity":{"id":"a8093e02-6e69-592d-a171-f0821c802e28","slug":"propionylcarnitine","display_name":"Propionylcarnitine","entity_type_key":"small_molecule"},"role":"negative comparator","stoichiometry":null,"state_label":"","sequence_order":7,"notes":""},{"entity":{"id":"66c9426e-baec-5089-b163-790e752c45c2","slug":"butyrylcarnitine","display_name":"Butyryl-L-carnitine","entity_type_key":"small_molecule"},"role":"negative comparator","stoichiometry":null,"state_label":"","sequence_order":8,"notes":""}]},"contexts":[{"dimension":"availability_state","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null},{"dimension":"evidence_access","value_text":"Primary full text: relevant Results/Methods and figure descriptions reviewed; supplements only where explicitly stated.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Human HR-proficient CCNE1 cancer-cell models; Results and supplementary Fig. 3.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"interpretation_status","value_text":"Source-derived curation with stated access limits; ungraded, not independent replication.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Acetyl-L-carnitine collection; exact intervention and molecular form govern interpretation.","comparator":null,"unit":null,"notes":"","entity":{"slug":"acetylcarnitine","display_name":"Acetyl-L-carnitine","entity_type_key":"small_molecule"}},{"dimension":"plain_language","value_text":"ALCAR reversed increased sensitivity to DNA-damaging agents caused by disruption of the alpha-ketoglutarate–carnitine axis.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"αKG-mediated carnitine synthesis drives DNA repair via histone acetylation. | https://pubmed.ncbi.nlm.nih.gov/42203879/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC13307467/ | https://doi.org/10.1038/s41586-026-10584-7","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"source_locator","value_text":"Reviewed reference cancer-drug-rescue; The study tested distinct upstream restrictions including IDH1 inhibition, glutamine starvation and TMLHE knockdown. Propionylcarnitine and butyrylcarnitine did not reproduce this rescue. This is a context-qualified summary of rescue contrasts, not an isolated basal ALCAR effect.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"trigger_kind","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null}],"evidence":[{"id":"172c3e27-5b36-52a5-826c-1bac2a9eecab","evidence_kind":"source_excerpt","locator":"Lines 336-342","start_line":336,"end_line":342,"excerpt":"### cancer-drug-rescue\n\nALCAR reversed increased sensitivity to DNA-damaging agents caused by disruption of the alpha-ketoglutarate–carnitine axis.\nThe study tested distinct upstream restrictions including IDH1 inhibition, glutamine starvation and TMLHE knockdown. Propionylcarnitine and butyrylcarnitine did not reproduce this rescue. This is a context-qualified summary of rescue contrasts, not an isolated basal ALCAR effect.\nModel and exposure: Human HR-proficient CCNE1 cancer-cell models; Results and supplementary Fig. 3.\nLimitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.\nReference: αKG-mediated carnitine synthesis drives DNA repair via histone acetylation. | 2026 | https://pubmed.ncbi.nlm.nih.gov/42203879/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC13307467/ | https://doi.org/10.1038/s41586-026-10584-7 | Access: Primary full text: relevant Results/Methods and figure descriptions reviewed; supplements only where explicitly stated.","model_system":"Human HR-proficient CCNE1 cancer-cell models; Results and supplementary Fig. 3.","directness":"reported_statement","verification_status":"source_recorded","notes":"Original paraphrase in the retained reviewed reference, not a verbatim primary-paper quotation. Access level is explicit.","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"2588f904-245a-597a-8a12-65118013fb90","stable_key":"import-e3f6ce02-0bd7-5103-acc1-68503ab6751b","title":"Acetyl-L-carnitine: detailed mechanisms of action (reviewed 6 October 2026)","document_type":"imported_text","citation_label":"AI-assisted original review of primary studies and clearly identified official records. Exact primary access is stated; no independent replication is claimed.","file_path":"","sha256":"84cc82d6fbb0fd5d73c4ce779e9f88e7f0184ba2d29b18ad0f153815380f2975","revision_id":"dac7a950-dbe5-5c7a-9c70-2ea711d5c71a","review_status":"source_recorded","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}