TY - JOUR
T1 - Temozolomide Resistance
T2 - A Multifarious Review on Mechanisms Beyond O-6-Methylguanine-DNA Methyltransferase
AU - Rao, Vanishree
AU - Kumar, Gautam
AU - Vibhavari, R. J.A.
AU - Nandakumar, Krishnadas
AU - Thorat, Nanasaheb D.
AU - Chamallamudi, Mallikarjuna Rao
AU - Kumar, Nitesh
N1 - Funding Information:
We thank the Manipal Academy of Higher Education for providing access to the Journals’ articles and providing Intramural funding (Ref. Letter No. MAHE/DREG/PHD/2019 dated February 7, 2019, Principal Investigator Dr. Nitesh Kumar). We also thank the All-India Council for Technical Education (AICTE), Government of India, New Delhi, for providing a National Doctoral Fellowship to Mr. Gautam Kumar (Application No. 53120).
Funding Information:
We thank the Manipal Academy of Higher Education for providing access to the journals’ articles and providing intramural funding. We also thank the All-India Council for Technical Education (AICTE), Government of India, New Delhi, for providing a National Doctoral Fellowship to Mr. Gautam Kumar.
Funding Information:
We thank the Department of Pharmaceuticals, Ministry of Chemicals and Fertilizers, and the Government of India for providing support to this work.
Publisher Copyright:
© 2023 Bentham Science Publishers.
PY - 2023
Y1 - 2023
N2 - Background: Chemotherapy with the oral alkylating agent temozolomide still prevails as a linchpin in the therapeutic regimen of glioblastoma alongside radiotherapy. Because of the impoverished prognosis and sparse chemotherapeutic medicaments associated with glioblastoma, the burgeoning resistance to temozolomide has made the whole condition almost irremediable. Objective: The present review highlights the possible mechanisms of drug resistance following chemotherapy with temozolomide. Methods: The review summarizes the recent developments, as published in articles from Scopus, PubMed, and Web of Science search engines. Description: One of the prime resistance mediators, O-6-methylguanine-DNA methyltransferase, upon activation, removes temozolomide-induced methyl adducts bound to DNA and reinstates genomic integrity. In the bargain, neoteric advances in the conception of temozolomide resistance have opened the door to explore several potential mediators like indirect DNA repair systems, efflux mechanisms, epigenetic modulation, microenvironmental influences, and autophagy-apoptosis processes that constantly lead to the failure of chemotherapy. Conclusion: This review sheds light on recent discoveries, proposed theories, and clinical developments in the field of temozolomide resistance to summarize the complex and intriguing involvement of oncobiological pathways.
AB - Background: Chemotherapy with the oral alkylating agent temozolomide still prevails as a linchpin in the therapeutic regimen of glioblastoma alongside radiotherapy. Because of the impoverished prognosis and sparse chemotherapeutic medicaments associated with glioblastoma, the burgeoning resistance to temozolomide has made the whole condition almost irremediable. Objective: The present review highlights the possible mechanisms of drug resistance following chemotherapy with temozolomide. Methods: The review summarizes the recent developments, as published in articles from Scopus, PubMed, and Web of Science search engines. Description: One of the prime resistance mediators, O-6-methylguanine-DNA methyltransferase, upon activation, removes temozolomide-induced methyl adducts bound to DNA and reinstates genomic integrity. In the bargain, neoteric advances in the conception of temozolomide resistance have opened the door to explore several potential mediators like indirect DNA repair systems, efflux mechanisms, epigenetic modulation, microenvironmental influences, and autophagy-apoptosis processes that constantly lead to the failure of chemotherapy. Conclusion: This review sheds light on recent discoveries, proposed theories, and clinical developments in the field of temozolomide resistance to summarize the complex and intriguing involvement of oncobiological pathways.
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U2 - 10.2174/1871527321666220404180944
DO - 10.2174/1871527321666220404180944
M3 - Review article
C2 - 35379142
AN - SCOPUS:85144977168
SN - 1871-5273
VL - 22
SP - 817
EP - 831
JO - CNS and Neurological Disorders - Drug Targets
JF - CNS and Neurological Disorders - Drug Targets
IS - 6
ER -