期刊
BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER
卷 1876, 期 2, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.bbcan.2021.188616
关键词
Glioblastoma multiforme; Temozolomide; Drug resistance; O-6-methylguanine-DNA methyltransferase (MGMT); Autophagy; Glioma stem cells (GSCs); miRNAs; Combination therapy
资金
- University Grants Commission, Government of India
- Science and Engineering Research Board [EMR/2016/005009]
- CCRH-Ministry of AYUSH, Government of India
- KGMU intramural grant
This review highlights various mechanisms behind TMZ resistance, including DNA repair, miRNA involvement, drug efflux, stem cells, etc., and proposes multiple strategies for successful treatment.
Temozolomide (TMZ) is a first-choice alkylating agent inducted as a gold standard therapy for glioblastoma multiforme (GBM) and astrocytoma. A majority of patients do not respond to TMZ during the course of their treatment. Activation of DNA repair pathways is the principal mechanism for this phenomenon that detaches TMZ-induced 0-6-methylguanine adducts and restores genomic integrity. Current understanding in the domain of oncology adds several other novel mechanisms of resistance such as the involvement of miRNAs, drug efflux transporters, gap junction's activity, the advent of glioma stem cells as well as upregulation of cell survival autophagy. This review describes a multifaceted account of different mechanisms responsible for the intrinsic and acquired TMZ-resistance. Here, we summarize different strategies that intensify the TMZ effect such as MGMT inhibition, development of novel imidazotetrazine analog, and combination therapy; with an aim to incorporate a successful treatment and increased overall survival in GBM patients.
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