PARP Inhibitors in Glioma: A Review of Therapeutic Opportunities

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 remaine...

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Bibliographic Details
Published in:Cancers 2022-02, Vol.14 (4), p.1003
Main Authors: Sim, Hao-Wen, Galanis, Evanthia, Khasraw, Mustafa
Format: Article
Language:English
Subjects:
Apoptosis
Blood-brain barrier
Brain cancer
Brain tumors
Breast cancer
Cancer therapies
Chemotherapy
Clinical trials
Cytotoxicity
Deoxyribonucleic acid
DNA
DNA damage
DNA methylation
DNA repair
Drugs
Enzymes
Glioblastoma
Glioma
Homologous recombination
Immunotherapy
Isocitrate dehydrogenase
Lethality
Mutation
Nervous system
Neurosurgery
Oncology
Ovarian cancer
Pancreatic cancer
Poly(ADP-ribose)
Poly(ADP-ribose) polymerase
Prostate cancer
Radiation therapy
Review
Ribose
Tumor microenvironment
Tumors
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Summary: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 ( ) 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.
ISSN:2072-6694
2072-6694
DOI:10.3390/cancers14041003