PMID- 38542190
OWN - NLM
STAT- MEDLINE
DCOM- 20240329
LR  - 20240330
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 25
IP  - 6
DP  - 2024 Mar 12
TI  - A Review of Approaches to Potentiate the Activity of Temozolomide against 
      Glioblastoma to Overcome Resistance.
LID - 10.3390/ijms25063217 [doi]
LID - 3217
AB  - A glioblastoma (GBM) is one of the most aggressive, infiltrative, and 
      treatment-resistant malignancies of the central nervous system (CNS). The current 
      standard of care for GBMs include maximally safe tumor resection, followed by 
      concurrent adjuvant radiation treatment and chemotherapy with the DNA alkylating 
      agent temozolomide (TMZ), which was approved by the FDA in 2005 based on a 
      marginal increase (~2 months) in overall survival (OS) levels. This treatment 
      approach, while initially successful in containing and treating GBM, almost 
      invariably fails to prevent tumor recurrence. In addition to the limited 
      therapeutic benefit, TMZ also causes debilitating adverse events (AEs) that 
      significantly impact the quality of life of GBM patients. Some of the most common 
      AEs include hematologic (e.g., thrombocytopenia, neutropenia, anemia) and 
      non-hematologic (e.g., nausea, vomiting, constipation, dizziness) toxicities. 
      Recurrent GBMs are often resistant to TMZ and other DNA-damaging agents. Thus, 
      there is an urgent need to devise strategies to potentiate TMZ activity, to 
      overcome drug resistance, and to reduce dose-dependent AEs. Here, we analyze 
      major mechanisms of the TMZ resistance-mediated intracellular signaling 
      activation of DNA repair pathways and the overexpression of drug transporters. We 
      review some of the approaches investigated to counteract these mechanisms of 
      resistance to TMZ, including the use of chemosensitizers and drug delivery 
      strategies to enhance tumoral drug exposure.
FAU - Karve, Aniruddha S
AU  - Karve AS
AUID- ORCID: 0000-0002-1617-4828
AD  - Division of Pharmaceutical Sciences, James L. Winkle College of Pharmacy, 
      University of Cincinnati, Cincinnati, OH 45267, USA.
FAU - Desai, Janki M
AU  - Desai JM
AUID- ORCID: 0000-0002-8673-1327
AD  - Division of Pharmaceutical Sciences, James L. Winkle College of Pharmacy, 
      University of Cincinnati, Cincinnati, OH 45267, USA.
FAU - Gadgil, Sidharth N
AU  - Gadgil SN
AD  - Division of Pharmaceutical Sciences, James L. Winkle College of Pharmacy, 
      University of Cincinnati, Cincinnati, OH 45267, USA.
FAU - Dave, Nimita
AU  - Dave N
AD  - Division of Pharmaceutical Sciences, James L. Winkle College of Pharmacy, 
      University of Cincinnati, Cincinnati, OH 45267, USA.
AD  - Lapix Therapeutics, Cambridge, MA 02142, USA.
FAU - Wise-Draper, Trisha M
AU  - Wise-Draper TM
AD  - Division of Hematology/Oncology, University of Cincinnati College of Medicine, 
      Cincinnati, OH 45267, USA.
FAU - Gudelsky, Gary A
AU  - Gudelsky GA
AD  - Division of Pharmaceutical Sciences, James L. Winkle College of Pharmacy, 
      University of Cincinnati, Cincinnati, OH 45267, USA.
FAU - Phoenix, Timothy N
AU  - Phoenix TN
AD  - Division of Pharmaceutical Sciences, James L. Winkle College of Pharmacy, 
      University of Cincinnati, Cincinnati, OH 45267, USA.
FAU - DasGupta, Biplab
AU  - DasGupta B
AD  - Division of Oncology, Cincinnati Children's Hospital, Cincinnati, OH 45229, USA.
FAU - Yogendran, Lalanthica
AU  - Yogendran L
AD  - Department of Neurology & Rehabilitation Medicine, University of Cincinnati 
      College of Medicine, Cincinnati, OH 45267, USA.
FAU - Sengupta, Soma
AU  - Sengupta S
AUID- ORCID: 0000-0003-4577-1397
AD  - Department of Neurology, School of Medicine, University of North Carolina, Chapel 
      Hill, NC 27514, USA.
AD  - Department of Neurosurgery, School of Medicine, University of North Carolina, 
      Chapel Hill, NC 27514, USA.
FAU - Plas, David R
AU  - Plas DR
AUID- ORCID: 0000-0001-7568-1400
AD  - Department of Cancer Biology, University of Cincinnati College of Medicine, 
      Cincinnati, OH 45267, USA.
FAU - Desai, Pankaj B
AU  - Desai PB
AD  - Division of Pharmaceutical Sciences, James L. Winkle College of Pharmacy, 
      University of Cincinnati, Cincinnati, OH 45267, USA.
LA  - eng
GR  - 1R61NS128232/National Institute of Neurological Disorders and Stroke (NINDS/NIH)/
GR  - University of Cincinnati Brain Tumor Center/
PT  - Journal Article
PT  - Review
DEP - 20240312
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - YF1K15M17Y (Temozolomide)
RN  - 0 (Antineoplastic Agents, Alkylating)
RN  - 9007-49-2 (DNA)
SB  - IM
MH  - Humans
MH  - Temozolomide/pharmacology/therapeutic use
MH  - *Glioblastoma/metabolism
MH  - Antineoplastic Agents, Alkylating/adverse effects
MH  - Quality of Life
MH  - *Brain Neoplasms/pathology
MH  - Neoplasm Recurrence, Local/drug therapy
MH  - DNA/pharmacology
MH  - Drug Resistance, Neoplasm/genetics
MH  - Cell Line, Tumor
PMC - PMC10970334
OTO - NOTNLM
OT  - combination therapeutics
OT  - glioblastoma
OT  - treatment resistance
COIS- Author Nimita Dave was employed by the company Lapix Therapeutics. The remaining 
      authors declare that the research was conducted in the absence of any commercial 
      or financial relationships that could be construed as a potential conflict of 
      interest.
EDAT- 2024/03/28 06:45
MHDA- 2024/03/29 06:45
PMCR- 2024/03/12
CRDT- 2024/03/28 01:17
PHST- 2023/07/23 00:00 [received]
PHST- 2024/02/26 00:00 [revised]
PHST- 2024/03/04 00:00 [accepted]
PHST- 2024/03/29 06:45 [medline]
PHST- 2024/03/28 06:45 [pubmed]
PHST- 2024/03/28 01:17 [entrez]
PHST- 2024/03/12 00:00 [pmc-release]
AID - ijms25063217 [pii]
AID - ijms-25-03217 [pii]
AID - 10.3390/ijms25063217 [doi]
PST - epublish
SO  - Int J Mol Sci. 2024 Mar 12;25(6):3217. doi: 10.3390/ijms25063217.