Deficiency in the Treatment Description of mTOR Inhibitor Resistance in Medulloblastoma, a Systematic Review

• Published in: International journal of molecular sciences Vol. 23; no. 1; p. 464
• Main Authors: Alammar, Hajar, Nassani, Rayan, Alshehri, Mana M, Aljohani, Alaa A, Alrfaei, Bahauddeen M
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 31.12.2021; MDPI
• Subjects: Antineoplastic Agents - pharmacology; Autophagy; Brain cancer; Brain tumors; Cell cycle; Chemotherapy; Child; Clinical trials; Drug Resistance, Neoplasm - drug effects; Epigenetics; Gene expression; Growth factors; Health services; Humans; Immunosuppression; Inhibitors; Initiation factor eIF-4E; Kinases; Lymphocytes; Lymphocytes T; Medulloblastoma; Medulloblastoma - drug therapy; Metabolism; Metastasis; mTOR; Mutation; Neurogenesis; Pathogenesis; Pediatrics; Protein Kinase Inhibitors - pharmacology; Proteins; Rapamycin; resistance; Review; Stem cells; Survival; Systematic review; targeted therapy; TOR protein; TOR Serine-Threonine Kinases - antagonists & inhibitors; Tumors; mTOR; targeted therapy; medulloblastoma; resistance
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms23010464

Medulloblastoma is a common fatal pediatric brain tumor. More treatment options are required to prolong survival and decrease disability. mTOR proteins play an essential role in the disease pathogenesis, and are an essential target for therapy. Three generations of mTOR inhibitors have been developed and are clinically used for immunosuppression and chemotherapy for multiple cancers. Only a few mTOR inhibitors have been investigated for the treatment of medulloblastoma and other pediatric tumors. The first-generation mTOR, sirolimus, temsirolimus, and everolimus, went through phase I clinical trials. The second-generation mTOR, AZD8055 and sapanisertib, suppressed medulloblastoma cell growth; however, limited studies have investigated possible resistance pathways. No clinical trials have been found to treat medulloblastoma using third-generation mTOR inhibitors. This systematic review highlights the mechanisms of resistance of mTOR inhibitors in medulloblastoma and includes IDO1, T cells, Mnk2, and eIF4E, as they prolong malignant cell survival. The findings promote the importance of combination therapy in medulloblastoma due to its highly resistant nature.