Glioblastoma Drug Discovery Service
Glioblastoma is a prevalent primary malignant tumor in the central nervous system derived from astrocytes. The clinical symptoms of glioblastoma are progressive neurological dysfunctions, including problems in eating and vision, headaches, vomiting, and seizures. Creative Biolabs has a long-term dedication to providing a range of life science services. Our experts in the field of neuroscience integrate global resources and technologies, which enable researchers to utilize our one-stop solutions to better understand the pathological mechanisms of glioblastoma, and therefore develop novel therapeutics, such as gene therapy and immunotherapy.
The molecular mechanism of glioblastoma is complex accompanied by the dysregulation of several signaling pathways. Due to the selective blood-brain barrier (BBB) permeability, nearly all chemotherapeutic substances are unable to access the tumor site. The stem-like cells used to treat tumors are known to lead to glioblastoma chemoresistance. Therefore, Creative Biolabs integrates global resources to help researchers investigate the basic mechanisms of action (MoA) to explain cell migration and invasion in glioblastoma.
Mechanism of Action Studies in Glioblastoma
The pathogenesis of glioblastoma is associated with genetic factors as well as dysregulations of multiple signaling pathways. Primary glioblastoma is mostly related to the amplification and mutation of the epidermal growth factor receptor (EGFR) gene, which leads to enhanced abnormal cell proliferation and survival via the EGFR-phosphatidylinositol3-kinase (PI3K) pathway. Besides, mutations of the cyclin-dependent kinase inhibitor 2A (CDKN2A) gene, isocitrate dehydrogenase (IDH) gene, and O6-methylguanine DNA methyltransferase (MGMT) gene are all involved in glioblastoma pathogenesis. Multiple molecular signaling pathways participate in glioblastoma. EGFR/Akt (protein kinase B)/phosphatase and tensin homolog (PTEN) pathway is involved in cellular proliferation and survival as well as G1 cell cycle arrest and apoptosis. The activation of the protein kinase C (PKC) pathway enhances gene expression, cell differentiation, proliferation, and survival as well as cell migration. The mutation of the p53 pathway leads to the dysfunctions of DNA and cell duplication. Dysfunction of retinoblastoma (RB) in the RB signaling pathway leads to uncontrolled cell differentiation, as RB protein is responsible for preventing cell proliferation by arresting the cell cycle in the G1-S phase. Vascular endothelial growth factor (VEGF) is involved in angiogenesis and vascular permeability, which is also important in glioblastoma pathogenesis.
Fig.1 Molecular targets of antiangiogenic therapies investigated in glioblastoma. (Wick, 2011)
Current Therapies for Glioblastoma
- Maximal surgical resection
- Radiotherapy plus concomitant and maintenance temozolomide (TMZ) chemotherapy
- Targeted therapy: antiangiogenic therapeutic strategies with monoclonal antibody bevacizumab
- Combined modality therapy
Glioblastoma Solutions at Creative Biolabs
Understanding the pathogenesis of glioblastoma and the limitations of existing therapeutic approaches make the challenge of exploring prospective treatments more urgent. According to the current MoA studies, targeting PKC, EGFR, rapamycin (mTOR), p53, etc. are also promising therapeutic strategies in glioblastoma. You can find reliable customized discovery services for glioblastoma target exploration and drug screening at Creative Biolabs with advanced technologies and research platforms. In addition, we provide one-stop solutions for further glioblastoma MoA studies and preclinical drug discovery, including in vitro, in vivo, and ex vivo services with dependable glioblastoma cell culture, brain slice, and animal models. Detailed information about our brain tumor platform is as follows.
To learn more details about preclinical glioblastoma drug discovery solutions, please feel free to contact us.
Reference
- Wick, W.; et al. Pathway inhibition: emerging molecular targets for treating glioblastoma. Neuro-oncology. 2011, 13(6): 566-579.
