Vulnerability of IDH1-Mutant Cancers to Histone Deacetylase Inhibition via Orthogonal Suppression of DNA Repair
Dow J, Krysztofiak A, Liu Y, Colon-Rios DA, Rogers FA, Glazer PM. Vulnerability of IDH1-Mutant Cancers to Histone Deacetylase Inhibition via Orthogonal Suppression of DNA Repair. Molecular Cancer Research 2021, 19: 2057-2067. PMID: 34535560, PMCID: PMC8642278, DOI: 10.1158/1541-7786.mcr-21-0456.Peer-Reviewed Original ResearchConceptsHistone deacetylase inhibitor vorinostatPatient-derived tumor xenograftsHomology-directed repairIsocitrate dehydrogenase 1/2 mutationsHistone deacetylase inhibitionIDH1 mutant cellsGreater cell deathHDACi treatmentInhibitor vorinostatTumor xenograftsDeacetylase inhibitionIDH1/2 mutationsPotential biomarkersSpecific cancersMutant cancersCancerCancer cellsDNA repair defectsMalignancyVorinostatDNA double-strand breaksGliomasHistone hypermethylationCell deathPARPiDirect targeting of amplified gene loci for proapoptotic anticancer therapy
Kaushik Tiwari M, Colon-Rios DA, Tumu HCR, Liu Y, Quijano E, Krysztofiak A, Chan C, Song E, Braddock DT, Suh HW, Saltzman WM, Rogers FA. Direct targeting of amplified gene loci for proapoptotic anticancer therapy. Nature Biotechnology 2021, 40: 325-334. PMID: 34711990, PMCID: PMC8930417, DOI: 10.1038/s41587-021-01057-5.Peer-Reviewed Original ResearchConceptsDNA double-strand breaksTriplex-forming oligonucleotidesDNA damage responseDouble-strand breaksDrug resistanceGene amplificationP53-independent apoptosisHER2-positive breastOvarian cancer modelHuman tumor xenograftsInduction of apoptosisGenomic lociNumber of drugsCellular functionsDamage responseGene locusProtein productsHER2-positive cancer cellsDriver genesClinical efficacyCombat drug resistanceDNA damageHER2 amplificationTherapeutic strategiesTumor xenografts