Olaparib for IDH+ gliomas – pro
Although low-grade gliomas that have an IDH mutation are typically more sensitive to chemotherapy than those that lack the mutation, the disease tends to come back as a more aggressive tumor after treatment. IDH mutations weaken the ability of glioma cells to repair DNA. Moreover this weakness can be exploited with the use of PARP inhibitors. that PARP inhibitors killed glioma cells with IDH mutations but not cells with normThere is only one phase I trial, the OPERATIC trial IDH. PARP inhibitor enhanced the toxic effects of chemotherapy treatment on IDH-mutant cells. Follow-up studies are expected to begin to study these early indications of effectiveness.
Y. Lu et al, Chemosensitivity of IDH1-Mutated Gliomas Due to an Impairment in PARP1-Mediated DNA Repair.Cancer Res. 2017 Apr 1;77(7):1709-1718.
Sulkowski PL et al, 2-Hydroxyglutarate produced by neomorphic IDH mutations suppresses homologous recombination and induces PARP inhibitor sensitivity.
Sci Transl Med. 2017 Feb 1;9(375).
SER Halford et al, Results of the OPARATIC trial: A phase I dose escalation study of olaparib in combination with temozolomide (TMZ) in patients with relapsed glioblastoma (GBM). Journal of Clinical Oncology 35, no. 15_suppl (May 20, 2017) 2022-2022.