N-METHYLPURINE DNA GLYCOSYLASE AND POLYMERASE BETA AS BIOMARKERS FOR ALKYLATOR CHEMOTHERAPY POTENTIATION

摘要

Described herein is the finding that polymerase beta (Polbeta) and N-methylpurine DNA glycosylase (MPG) can be used as biomarkers to evaluate the sensitivity of a subject to combination therapy that includes treatment with either temozolomide (TMZ) and methoxyamine, or TMZ and a poly(ADP-ribose) polymerase (PARP) inhibitor. Thus, provided herein is a method of determining if a subject will be sensitive to TMZ and methoxyamine, or TMZ and a PARP inhibitor by measuring expression of Polbeta and MPG in a sample from the subject and comparing expression of Polbeta and MPG in the sample to a control. A decrease in expression of Polbeta and an increase in expression of MPG relative to the control indicates the subject is sensitive to TMZ and methoxyamine, or sensitive to TMZ and the PARP inhibitor.