Method of using histone deacetylase inhibitors and monitoring biomarkers in combination therapy

摘要

Provided herein are methods for using at least one histone deacetylase inhibitor to decrease cellular DNA repair activity, methods for monitoring the decrease of cellular DNA repair activity using at least one biomarker, methods of treating cancer by using at least one histone deacetylase inhibitor to decrease cellular DNA repair activity in combination therapy, methods of combination therapy where at least one histone deacetylase inhibitor interferes with a DNA repairing mechanism involving RAD51, methods for predicting a induction time period between a first administration of at least one histone deacetylase inhibitor and a second administration of at least one other therapeutic treatment, and pharmaceutical compositions for combination therapy.

主权项

1. A method of inhibiting or relieving a cancer associated with a defect in non-homologous end joining of DNA in an individual in need thereof, comprising: (a) identifying the cancer as containing a defect in non-homologous end joining of DNA, wherein the defect comprises a defect in a gene selected from the group consisting of: Ku70, Ku80, Ku86, Ku, PRKDC, LIG4, XRCC4, DCLRE1C, and XLF; and (b) administering to the individual: (i) a therapeutically effective amount of 3-((dimethylamino)methyl)-N-(2-(4-(hydroxycarbamoyl)phenoxy)ethyl)benzofuran-2-carboxamide, or a pharmaceutically acceptable salt thereof; and (ii) a treatment capable of damaging cellular DNA.