Schwannoma Drug Discovery Service

Creative Biolabs has accumulated years of experience in the field of neuroscience. We are a contract research organization, providing customized one-stop solutions that allow your research needs in neuroscience to be addressed and promote the process of schwannomas research from mechanistic to clinical translational studies. Our experienced neuroscientists are ready to design tailored solutions to meet your research requirements.

Background of Schwannoma

Schwannomas are common heterogeneous peripheral nerve sheath tumors, which occur spontaneously or are accompanied by inherited tumor syndromes, such as neurofibromatosis type 2 (NF2), schwannomatosis, and Carney's complex. Schwannomas are primarily benign tumors, rare of which undergo malignant transformation.

Mechanism of Action Studies of Schwannoma

Our platforms are supported by qualified academics and professional neural scientists. We are prepared to provide you with the latest expertise and accurate research data to help you explore the mechanism of schwannomas. Defects or inactivation of merlin encoded by the NF2 gene located on chromosome 22 are intimately associated with the pathogenesis of schwannomas, as the NF2 gene product, merlin, has tumor suppressor activity. Defects of the NF2 gene include gene mutations, allelic losses, deletions, and gene promoter hypermethylation. Merlin interacts with integrins and focal adhesion proteins, which participate in the inhibition of tyrosine kinase receptor (RTK) expression and signaling. The RTK signaling pathway is important in the normal function of cells, which is involved in the formation of intercellular junctions and contact inhibition of cell growth. Besides, merlin inhibits the E3 ubiquitin ligase CRL4-DCAF1 complex within the nucleus, which regulates the transcription of multiple genes. Dysfunction of merlin leads to abnormal cell proliferation and cell growth resulting in tumorigenesis. In addition, merlin can directly inhibit the mitogen‐activated protein kinase (MAPK), phosphatidylinositol 3‐kinase (PI3K), and the mammalian target of rapamycin (mTOR). Merlin loss increases the expression and signaling of growth factors for cell proliferation. The activated growth factor receptors impair adherens junctions and impact cell growth via the Wnt/catenin signaling pathway. The growth factor receptor activation stimulates downstream of the Ras/Mek/Erk and PI3K pathways.

Fig.1 Multiple growth promoting intracellular pathways are activated by a number of tyrosine kinase receptors. (Miller, 2014)

Schwannoma Solutions at Creative Biolabs

Schwannomas are common benign tumors of peripheral nerves. Although a majority of schwannomas may be asymptomatic and easily treated by surgical resection, deep‐seated and multiple schwannomas with genetic syndromes remain to explore novel treatments. The MoA studies in schwannoma have revealed multiple pathways in which merlin is involved. Merlin plays an important role at various receptors in the nucleus and cell membrane, which brings us new opportunities to explore therapeutic targeting approaches. Creative Biolabs has years of experience to provide a wide range of in vitro, in vivo, and ex vivo services as well as discovery and development services for schwannoma research and development. We provide advanced technologies and research platforms with multiple cell culture models and animal models to satisfy your research and development demands. We provide discovery services for following therapeutic targets based on the pathogenesis of schwannoma related to merlin may drive the process of treatment development.

• Growth factor receptor
• Epidermal growth factor receptor (EGFR)
• Platelet‐derived growth factor receptor β (PDGFRβ)
• Insulin‐like growth factor receptor (IGF 1R)
• Vascular endothelial growth factor (VEGF) and its receptor

The following scheme demonstrates our preclinical translational research platforms for the targeted therapy development of schwannoma.

For further schwannoma MoA studies and preclinical drug discovery and development at Creative Biolabs, please directly contact us for more information.

Reference

1. Miller, C.; et al. Vestibular Schwannoma Drug Development: Current State-of-the Art. Current Otorhinolaryngology Reports. 2014, 2(4): 217-225.