Work

Mechanisms of temozolomide resistance in glioblastoma - a comprehensive review

Year: 2020

Type: article

Abstract: Glioblastoma (GBM) is the most common primary malignant brain tumor in adults and has an exceedingly low median overall survival of only 15 months. Current standard-of-care for GBM consists of gross total surgical resection followed by radiation with concurrent and adjuvant chemotherapy. Temozolomide (TMZ) is the first-choice chemotherapeutic agent in GBM; however, the development of resistance to TMZ often becomes the limiting factor in effective treatment. While O6-methylguanine-DNA methyltransferase repair activity and uniquely resistant populations of glioma stem cells are the most well-known contributors to TMZ resistance, many other molecular mechanisms have come to light in recent years. Key emerging mechanisms include the involvement of other DNA repair systems, aberrant signaling pathways, autophagy, epigenetic modifications, microRNAs, and extracellular vesicle production. This review aims to provide a comprehensive overview of the clinically relevant molecular mechanisms and their extensive interconnections to better inform efforts to combat TMZ resistance.

Source: Cancer Drug Resistance

DOI: 10.20517/cdr.2020.79

Authors: Neha Singh, Alexandra Miner, Lauren Hennis, Sandeep Mittal

Institutions: Carilion Clinic, Virginia Tech

Language: English

Topic: Glioma Diagnosis and Treatment

Subfield: Oncology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: diamond

Funder: National Cancer Institute