S. Gueble

Biomarker-Targeted O6-Guanine Alkylation Potentiates ATR Inhibitor Response in De Novo and Relapsed/Refractory AML

Targeting O6-methylguanine-DNA methyltransferase deficiency in preclinical models of extracranial human cancers with a tumor-selective DNA modifying agent

Temozolomide (TMZ) is an established therapy for gliomas with silencing of the DNA repair protein O6-methylguanine-DNA methyltransferase (MGMT) but is hindered by the frequent development of resistance via loss of mismatch repair (MMR) proteins. To overcome this resistance, a novel 2-fluoroethylating agent, KL-50, was...

Abstract A060: Targeting metabolic–DNA repair vulnerabilities in SDHB- and FH-deficient renal cell carcinoma with the novel alkylating agent KL-50

FH- and SDHB-mutant RCC is identified as a molecularly defined subset characterised by epigenetic MGMT silencing, which may confer selective vulnerability to KL-50, which has the potential to overcome resistance mechanisms that have historically constrained the clinical utility of TMZ in this disease context.