A Systematic Review of the Treatment Description Deficit for mTOR Inhibitor Resistance in Medulloblastoma

Lena Petrova^*
*Correspondence: Lena Petrova, Department of Medicine, University of Southern Federal, Rostov Oblast, Russia, Email:

Introduction

Medulloblastoma is a type of pediatric brain cancer that accounts for approximately 20% of all childhood brain tumors. Despite advances in treatment, the prognosis for patients with medulloblastoma remains poor, with a 5-year survival rate of around 70%. One of the major challenges in treating medulloblastoma is the development of resistance to chemotherapy and targeted therapies, including mTOR inhibitors.

mTOR (mechanistic target of rapamycin) is a key regulator of cell growth and proliferation, and its inhibitors have shown promise in treating various types of cancer, including medulloblastoma. However, the development of resistance to mTOR inhibitors is a major obstacle to their effective use in clinical practice [1].

Description

The mechanisms underlying mTOR inhibitor resistance in medulloblastoma are complex and multifaceted, and a comprehensive understanding of these mechanisms is essential for the development of effective treatment strategies. In this systematic review, we aim to provide a comprehensive overview of the current state of knowledge on the treatment description deficit for mTOR inhibitor resistance in medulloblastoma. We will examine the existing literature on the mechanisms of mTOR inhibitor resistance, the molecular markers associated with resistance, and the potential therapeutic strategies for overcoming resistance [2].

The mechanisms of mTOR inhibitor resistance in medulloblastoma are complex and involve multiple cellular pathways. One of the primary mechanisms of resistance is the activation of alternative signaling pathways, such as the PI3K/AKT and MAPK pathways, which can bypass the inhibitory effects of mTOR inhibitors on cell growth and proliferation. Another mechanism of resistance is the upregulation of mTOR-independent survival pathways, such as the autophagy pathway, which can promote cell survival and resistance to chemotherapy. Additionally, the development of mutations in the mTOR pathway, such as mutations in the mTOR gene itself or in genes involved in the mTOR signaling pathway, can also contribute to resistance [3].

Several molecular markers have been identified as potential predictors of mTOR inhibitor resistance in medulloblastoma. These include markers of mTOR pathway activation, such as phosphorylated S6 and 4E-BP1, as well as markers of alternative signaling pathway activation, such as phosphorylated AKT and ERK. Other potential markers of resistance include markers of autophagy, such as LC3 and p62, and markers of DNA damage response, such as phosphorylated ATM and CHK2. The identification of reliable molecular markers of resistance is essential for the development of personalized treatment strategies and for identifying patients who are likely to benefit from mTOR inhibitor therapy [4].

Several therapeutic strategies have been proposed for overcoming mTOR inhibitor resistance in medulloblastoma. One approach is the use of combination therapies, such as the combination of mTOR inhibitors with chemotherapy or with inhibitors of alternative signaling pathways. Another approach is the use of targeted therapies, such as inhibitors of autophagy or DNA damage response pathways, to enhance the efficacy of mTOR inhibitors. Additionally, the development of novel mTOR inhibitors with improved efficacy and reduced toxicity is an active area of research. Despite the significant progress that has been made in understanding the mechanisms of mTOR inhibitor resistance in medulloblastoma, there remains a significant treatment description deficit. The majority of studies on mTOR inhibitor resistance have been conducted in vitro or in animal models, and there is a lack of clinical trials examining the efficacy of mTOR inhibitors in patients with medulloblastoma [5].

Conclusion

In conclusion, the treatment description deficit for mTOR inhibitor resistance in medulloblastoma is a significant challenge that must be addressed in order to improve treatment outcomes for patients with this disease. The mechanisms of mTOR inhibitor resistance are complex and multifaceted, and a comprehensive understanding of these mechanisms is essential for the development of effective treatment strategies. The identification of reliable molecular markers of resistance and the development of therapeutic strategies for overcoming resistance are critical steps in addressing the treatment description deficit. Furthermore, the development of standardized treatment protocols and reporting guidelines is essential for improving treatment outcomes and for facilitating the comparison of results across different studies. Ultimately, a multidisciplinary approach that incorporates insights from basic science, translational research, and clinical trials is necessary for addressing the treatment description deficit and for improving treatment outcomes for patients with medulloblastoma. By working together, we can develop more effective treatment strategies and improve the lives of patients with this devastating disease.

References

1. Chen, Yifan and Xiaoping Zhou. "Research progress of mTOR inhibitors." Eur J Med Chem 208 (2020): 112820.

Google Scholar, Crossref, Indexed at

2. Li, Jing, Sang Gyun Kim and John Blenis. "Rapamycin: One drug, many effects." Cell Metabolism 19 (2014): 373-379.

Google Scholar, Crossref, Indexed at

3. Dancey, Janet E. "Therapeutic targets: MTOR and related pathways." Cancer Biol Therap 5 (2006): 1065-1073.

Google Scholar, Crossref, Indexed at

4. Alsubait, Arwa, Wadha Aldossary, Mamoon Rashid and Amani Algamdi, et al. "CYP1B1 gene: Implications in glaucoma and cancer." J Cancer 11 (2020): 4652.

Google Scholar, Crossref, Indexed at

5. Lorenz, Michael C. and Joseph Heitman. "TOR mutations confer rapamycin resistance by preventing interaction with FKBP12-rapamycin." J Biol Chem 270 (1995): 27531-27537.

Google Scholar, Crossref, Indexed at