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

被引:8
作者
Alammar, Hajar [1 ]
Nassani, Rayan [2 ]
Alshehri, Mana M. [2 ]
Aljohani, Alaa A. [1 ]
Alrfaei, Bahauddeen M. [1 ,2 ]
机构
[1] King Saud bin Abdulaziz Univ Hlth Sci, Coll Med, Minist Natl Guard Hlth Affairs, Riyadh 11426, Saudi Arabia
[2] King Saud bin Abdulaziz Univ Hlth Sci KSAU HS, Dept Cellular Therapy & Canc Res, King Abdullah Int Med Res Ctr, Minist Natl Guard Hlth Affairs, Riyadh 11426, Saudi Arabia
关键词
mTOR; medulloblastoma; targeted therapy; resistance; TESTING STAGE 1; KINASE INHIBITOR; CONFERS RESISTANCE; SOLID TUMORS; PATHWAY; TARGET; TEMSIROLIMUS; GROWTH; CLASSIFICATION; COMBINATION;
D O I
10.3390/ijms23010464
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
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页数:14
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