SELECTIVE TREATMENT OF CANCERS HAVING HISTONE H3 MUTATIONS OR ABERRANT LEVELS OF DNA OR HISTONE METHYLATION, ACETYLATION OR DEFECTS IN HOMOLOGOUS RECOMBINATION

摘要

The invention concerns compositions and a method for treating or delaying the onset, progression, or relapse of a cancer in a subject, the method comprising administering, optionally with radiation therapy, an inhibitor of: (a) DNA-Dependent Protein Kinase catalytic subunit, and an inhibitor of Poly-ADP Ribose Polymerase, wherein the cancer has a histone H3.3 mutation or is a homologous recombination-defective (HR-defective) cancer; or (b) wild-type isocitrate dehydrogenase, wherein the IDH inhibitor is administered in an effective amount to decrease wild-type IDH activity in cells of the cancer, and wherein the cancer carries a histone H3.3 K27M mutation, and/or the cancer has low DNA methylation and/or low histone methylation; or (c) histone acetyltransferase, wherein the cancer carries a histone H3.3 K27M mutation, and/or high histone acetylation; or (d) histone deacetylase, wherein the cancer carries a histone H3.3 K27M mutation, and/or has high histone acetylation; or (e) any combination thereof.