PARP Inhibitors in Glioma: A Review of Therapeutic Opportunities

SIMPLE SUMMARY: There is a pressing need for new effective treatments against glioma. A promising option is a class of drugs called poly(ADP-Ribose) polymerase (PARP) inhibitors. PARP inhibitors block the repair of DNA damage. They may work synergistically with radiotherapy, chemotherapy and immunotherapy. They may work particularly well in settings where other DNA damage repair pathways are impaired. This article reviews the clinical trials investigating PARP inhibitors in glioma. ABSTRACT: Gliomas are the most common malignant primary brain tumor in adults. Despite advances in multimodality therapy, incorporating surgery, radiotherapy, systemic therapy, tumor treating fields and supportive care, patient outcomes remain poor, especially in glioblastoma where median survival has remained static at around 15 months, for decades. Low-grade gliomas typically harbor isocitrate dehydrogenase (IDH) mutations, grow more slowly and confer a better prognosis than glioblastoma. However, nearly all gliomas eventually recur and progress in a way similar to glioblastoma. One of the novel therapies being developed in this area are poly(ADP-Ribose) polymerase (PARP) inhibitors. PARP inhibitors belong to a class of drugs that target DNA damage repair pathways. This leads to synthetic lethality of cancer cells with coexisting homologous recombination deficiency. PARP inhibitors may also potentiate the cytotoxic effects of radiotherapy and chemotherapy, and prime the tumor microenvironment for immunotherapy. In this review, we examine the rationale and clinical evidence for PARP inhibitors in glioma and suggest therapeutic opportunities.