Abstract
The current standard of care in glioblastoma multiforme (GBM), as the most morbid brain tumor, is not adequate, despite substantial progress in cancer therapy. Among patients receiving current standard treatments, including surgery, irradiation, and chemotherapy, the overall survival (OS) period with GBM is less than one year. The high mortality frequency of GBM is due to its aggressive nature, including accelerated growth, deregulated apoptosis, and invasion into surrounding tissues. The understanding of the molecular pathogenesis of GBM is, therefore, crucial for identifying, designing, and repurposing potential agents in future therapeutic approaches. In recent decades, it has been apparent that several neurotransmitters, specifically substance P (SP), an undecapeptide in the family of neuropeptides tachykinins, are found in astrocytes. After binding to the neurokinin-1 receptor (NK-1R), the SP controls cancer cell growth, exerts antiapoptotic impacts, stimulates cell invasion/metastasis, and activates vascularization. Since SP/NK-1R signaling pathway is a growth driver in many cancers, this potential mechanism is proposed as an additional target for treating GBM. Following an evaluation of the function of both SP and its NK-1R inhibitors in neoplastic cells, we recommend a unique and promising approach for the treatment of patients with GBM.
Keywords: Glioblastoma multiforme, apoptosis, substance P, Neurokinin-1 receptor (NK-1R), GBM, NK1R antagonists.
Current Medicinal Chemistry
Title:Neurokinin-1 Receptor (NK-1R) Antagonists: Potential Targets in the Treatment of Glioblastoma Multiforme
Volume: 28 Issue: 24
Author(s): Amir R. Afshari, Ali Motamed-Sanaye, Hamed Sabri, Arash Soltani, Sepideh Karkon-Shayan, Sarvin Radvar, Hossein Javid, Hamid Mollazadeh, Thozhukat Sathyapalan and Amirhossein Sahebkar*
Affiliation:
- Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad,Iran
Keywords: Glioblastoma multiforme, apoptosis, substance P, Neurokinin-1 receptor (NK-1R), GBM, NK1R antagonists.
Abstract: The current standard of care in glioblastoma multiforme (GBM), as the most morbid brain tumor, is not adequate, despite substantial progress in cancer therapy. Among patients receiving current standard treatments, including surgery, irradiation, and chemotherapy, the overall survival (OS) period with GBM is less than one year. The high mortality frequency of GBM is due to its aggressive nature, including accelerated growth, deregulated apoptosis, and invasion into surrounding tissues. The understanding of the molecular pathogenesis of GBM is, therefore, crucial for identifying, designing, and repurposing potential agents in future therapeutic approaches. In recent decades, it has been apparent that several neurotransmitters, specifically substance P (SP), an undecapeptide in the family of neuropeptides tachykinins, are found in astrocytes. After binding to the neurokinin-1 receptor (NK-1R), the SP controls cancer cell growth, exerts antiapoptotic impacts, stimulates cell invasion/metastasis, and activates vascularization. Since SP/NK-1R signaling pathway is a growth driver in many cancers, this potential mechanism is proposed as an additional target for treating GBM. Following an evaluation of the function of both SP and its NK-1R inhibitors in neoplastic cells, we recommend a unique and promising approach for the treatment of patients with GBM.
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Afshari R. Amir, Motamed-Sanaye Ali , Sabri Hamed , Soltani Arash , Karkon-Shayan Sepideh , Radvar Sarvin , Javid Hossein, Mollazadeh Hamid , Sathyapalan Thozhukat and Sahebkar Amirhossein*, Neurokinin-1 Receptor (NK-1R) Antagonists: Potential Targets in the Treatment of Glioblastoma Multiforme, Current Medicinal Chemistry 2021; 28 (24) . https://dx.doi.org/10.2174/0929867328666210113165805
DOI https://dx.doi.org/10.2174/0929867328666210113165805 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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