A Review of Drug Therapy in Vestibular Schwannoma

Abstract

Vestibular schwannomas (VSs, also known as acoustic neuromas) are benign intracranial tumors commonly managed with observation, surgery, and radiotherapy. There is currently no approved pharmacotherapy for VS patients, which is why we conducted a detailed search of relevant literature from PubMed and Web of Science to explore recent advances and experiences in drug therapy. VSs feature a long course of disease that requires treatment to have minimal long-term side effects. Conventional chemotherapeutic agents are characterized by neurotoxicity or ototoxicity, poor effect on slow-growing tumors, and may induce new mutations in patients who have lost tumor suppressor function, and therefore are unsuitable for treating VSs. Along with the well-investigated molecular pathophysiology of VS and the increasingly accessible technology such as drug repositioning platform, many molecular targeted inhibitors have been identified and shown certain therapeutic effects in preclinical experiments or clinical trials.

Keywords:

• vestibular schwannomas
• drug therapy
• therapeutic targets
• VEGFR inhibitor

Acknowledgments

This study was Sponsored by Shanghai Sailing Program (19YF1405700), National Natural Science Foundation of China (NSFC81872938, 82003864).

Abbreviations

ATP, adenosine triphosphate; c-MET, c-mesenchymal-epithelial transition; CML, chronic myelogenous leukemia; COX2, cyclooxygenase 2; CSF1-R, colony-stimulating factor1-receptor; CXCR4, chemokine receptor-4; ERK, extracellular-signal-regulated kinases; FAK1, focal adhesion kinase 1; FGF, fibroblasts growth factor; Flk-2, fetal liver kinase-2; HDACIs, histone deacetylase inhibitors; HGF, hepatocyte growth factor; HSC, human Schwann cell; IGF1, insulin-like growth factor-1; IPA, Ingenuity Pathway Analysis; MD-MSC, merlin-deficient mouse Schwann cells; MEK, mitogen extracellular signal-regulated kinase; mTORC1, mammalian target of rapamycin complex 1; NF2, neurofibromatosis type 2; nrPTKs, non-receptor protein tyrosine kinases; NSAIDs, non-steroidal anti-inflammatory drugs; PAK, p21-activated kinase; PDGF, platelet-derived growth factor; PDK1, phosphoinositide-dependent kinase-1; PET/CT, positron emission tomography/computed tomography; PGE2, prostaglandin E2; Ph+ ALL, Philadelphia chromosome-positive acute lymphoblastic leukemia; PI3K, phosphoinositide 3-kinase; PTGS2, prostaglandin G/H synthase 2; PTK, protein tyrosine kinase; Raf, rapidly accelerated fibrosarcoma; Ras, retrovirus-associated DNA sequences; RTKs, receptor protein tyrosine kinases; SEMA3F, semaphoring3F; TNF, tumor necrosis factor; VEGF, vascular endothelial growth factor; VSs, vestibular schwannomas.

Disclosure

The authors report no conflicts of interest in this work.