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TK2 is a nuclear gene encoding the mitochondrial matrix protein thymidine kinase 2 (TK2), a critical enzyme in the mitochondrial nucleotide salvage pathway. Deficiency of TK2 activity causes mitochondrial DNA (mtDNA) depletion, which in humans manifests predominantly as a mitochondrial myopathy with onset typically in infancy and childhood. We previously showed that oral treatment of the Tk2 H126N knock-in mouse model (Tk2-/-) with the TK2 substrates, deoxycytidine (dCtd) and thymidine (dThd), delayed disease onset and prolonged median survival by 3-fold. Nevertheless, dCtd + dThd treated Tk2-/- mice showed mtDNA depletion in brain as early as postnatal day 13 and in virtually all other tissues at age 29 days.
Pubmed ID: 31383553
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Division of NCI that takes prospective cancer detection and treatment leads, facilitates their paths to clinical application, and expedites the initial and subsequent large-scale testing of new agents, biomarkers, imaging tests, and other therapeutic interventions (radiation, surgery, immunotherapy) in patients. DCTD, like all of NCI, supports many programs that could not be done without government funding - investigators supported by the division engage in scientifically sound, high-risk research that may yield great benefits for patients with cancer, but are too difficult or risky for industry or academia to pursue. This includes a particular emphasis on the development of distinct molecular signatures for cancer, refined molecular assays, and state-of-the-art imaging techniques that will guide oncologic therapy in the future. The division has eight major programs that work together to bring unique molecules, diagnostic tests, and therapeutic interventions from the laboratory bench to the patient bedside: * Cancer Diagnosis Program * Cancer Imaging Program * Cancer Therapy Evaluation Program * Developmental Therapeutics Program * Radiation Research Program * Translational Research Program * Biometrics Research Branch * Office of Cancer Complementary and Alternative Medicine
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