Aptamer-based conjugated molecules in experimental and clinical approaches to treatment of glioblastoma

Glioblastoma is the most common primary malignant tumor of nervous system and one of the most incurable human tumors. The median of overall survival is 16—17 months after comprehensive treatment. Among various difficulties for new therapeutic approaches, we should emphasize the blood-brain barrier complicating delivery of anti-cancer drugs to neoplasm and perifocal area. A promising approach is aptamer molecules as synthetic amino acid analogs capable of interacting and regulating activity of target proteins based on their spatial structural interactions. Aptamers possess high specificity and affinity to various receptors on cell surface and inside its structures if they penetrate cell membrane. In this review, we present various approaches to development of aptamer-based drugs against glioblastoma. Kopylov A.M. et al. synthesized a series of aptamers targeting EGFR and capable for delivery of toxic agents to tumor cells. Important clinical successes include the results of NOX-A12 drug and data on combined drugs based on trastuzumab in patients with metastatic breast cancer. NOX-A12 is an aptamer blocking CXCL-12 gene and reducing resistance to irradiation of glioblastoma cells. Furthermore, very high control of breast cancer brain metastases in HER-2 positive cases was demonstrated for trastuzumab-emtansine and trastuzumab-deruxtecan. The last finding indicates the perspective for aptamer targeting glioblastoma tumor cells in conjugation with emtansine or deruxtecan.