Unraveling the secrets of Medulloblastoma: a comprehensive review of molecular pathways associated with pathogenesis, therapeutic resistance and potential treatment strategies
DOI:
https://doi.org/10.61919/jhrr.v4i1.344Keywords:
Angiogenesis, Brain tumor, PI3K pathwayAbstract
Medulloblastoma is a highly emerging brain tumor mostly found in infants and children and is less observed in adults. Several genetic aberrations affect the normal signaling activity at an embryonal level and even after development. Various factors abrupt the normal processes which later become the hallmarks of cancer. The use of inhibitory drugs on those targets that become the site of tumor origin will help in dealing with early-stage diseases. Interactions across WNT and NOTCH signaling exhibit the ability to stimulate branching and modification of present arteries and veins in the surrounding tumor microenvironment. Cerebrospinal fluid (CSF) surrounding the primary tumor site is initially modified by tumor cells via Complement Component 3 which subsequently increases the entry of growth factors into the fluid. MB tumor cells then undergo Epithelial to Mesenchymal transition (EMT), allowing cells to disperse from the main tumor location and infiltrate CSF. The defects in DNA repair genes are potentially linked to development and response to therapy in errors within DNA repair genes that may play a role in MB progression and treatment resistance. CT and MRI scans are commonly used for the diagnosis of MB in patients. The exact mechanism behind MB is still poorly understood but certain immune and targeted therapies are applied to those pathways that provoke tumors. In the future, researchers are majorly focusing on understanding the exact mechanism so that it will help in the development of certain diagnostic and therapeutic techniques.
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Abadía-Molina, F., Morón-Calvente, V., Baird, S. D., Shamim, F., Martín, F., & MacKenzie,
A. (2017). Neuronal apoptosis inhibitory protein (NAIP) localizes to the cytokinetic machinery during cell division. Scientific Reports, 7(1), 1-12.
Audi, Z. F., Saker, Z., Rizk, M., Harati, H., Fares, Y., Bahmad, H. F., & Nabha, S. M. (2021). Immunosuppression in Medulloblastoma: Insights into Cancer Immunity and Immunotherapy. Current Treatment Options in Oncology, 22(9). https://doi.org/10.1007/s11864-021-00874-9
Bahmad, H. F., & Poppiti, R. J. (2020). Medulloblastoma cancer stem cells: molecular signatures and therapeutic targets. Journal of clinical pathology, 73(5), 243-249.
Boire, A., Zou, Y., Shieh, J., Macalinao, D. G., Pentsova, E., & Massagué, J. (2017). Complement Component 3 Adapts the Cerebrospinal Fluid for Leptomeningeal Metastasis. Cell, 168(6), 1101-1113.e13. https://doi.org/10.1016/j.cell.2017.02.025
Castriconi, R., Dondero, A., Negri, F., Bellora, F., Nozza, P., Carnemolla, B., Raso, A., Moretta, L., Moretta, A., & Bottino, C. (2007). Both CD133+ and CD133- medulloblastoma cell lines express ligands for triggering NK receptors and are susceptible to NK-mediated cytotoxicity. European Journal of Immunology, 37(11), 3190–3196. https://doi.org/10.1002/eji.200737546
Corada, M., Nyqvist, D., Orsenigo, F., Caprini, A., Taketo, M. M., Iruela-arispe, M. L., & Adams, R. H. (2021). HHS Public Access. 18(6), 938–949.
A. https://doi.org/10.1016/j.devcel.2010.05.006.The
Giatromanolaki, A., Koukourakis, M. I., Sivridis, E., Turley, H., Talks, K., Pezzella, F., Gatter,
A. K. C., & Harris, A. L. (2001). Relation of hypoxia-inducible factor 1α and 2α inoperable non-small cell lung cancer to angiogenic/molecular profile of tumors and survival. British Journal of Cancer, 85(6), 881–890. https://doi.org/10.1054/bjoc.2001.2018
Guan, G., Zhang, Y., Lu, Y., Liu, L., Shi, D., Wen, Y., Yang, L., Ma, Q., Liu, T., Zhu, X., Qiu, X., & Zhou, Y. (2015). The HIF-1α/CXCR4 pathway supports hypoxia-induced metastasis of human osteosarcoma cells. Cancer Letters, 357(1), 254–264. https://doi.org/10.1016/j.canlet.2014.11.034
Juraschka, K., & Taylor, M. D. (2019). Medulloblastoma in the age of molecular subgroups: A review article. Journal of Neurosurgery: Pediatrics, 24(4), 353-363.
Koeller, K. K., & Rushing, E. J. (2003). From the Archives of the AFIP - Medulloblastoma: A Comprehensive Review with Radiologic-Pathologic Correlation. Radiographics, 23(6), 1613–1637. https://doi.org/10.1148/rg.236035168
MacDonald, T. J.; Aguilera, D.; Castellino, R. C. (2014). The rationale for targeted therapies in medulloblastoma. Neuro-Oncology, 16(1), 9–20. doi:10.1093/neuonc/not147
Manoranjan, B., Venugopal, C., McFarlane, N., Doble, B. W., Dunn, S. E., Scheinemann, K., & Singh, S. K. (2012). Medulloblastoma stem cells: where development and cancer cross pathways. Pediatric Research, 71(2), 516-522.
Martirosian, V., Chen, T. C., Lin, M., & Neman, J. (2016). Medulloblastoma initiation and spread: Where neurodevelopment, microenvironment and cancer cross pathways. Journal of Neuroscience Research, 94(12), 1511–1519. https://doi.org/10.1002/jnr.23917
Millard, N. E., & De Braganca, K. C. (2016). Medulloblastoma. Journal of Child Neurology, 31(12), 1341–1353. https://doi.org/10.1177/0883073815600866
A. Northcott, P. A., Robinson, G. W., Kratz, C. P., Mabbott, D. J., Pomeroy, S. L., Clifford, S. C., ... & Pfister, S. M. (2019). Medulloblastoma. Nature reviews Disease primers, 5(1), 1-20.
Poretti, A., Meoded, A., & Huisman, T. A. G. M. (2012). Neuroimaging of pediatric posterior fossa tumors including review of the literature. Journal of Magnetic Resonance Imaging, 35(1), 32–47. https://doi.org/10.1002/jmri.22722.
Shaik, S., Maegawa, S., & Gopalakrishnan, V. (2021). Medulloblastoma: novel insights into emerging therapeutic targets. Expert Opinion on Therapeutic Targets, 25(8), 615–619. https://doi.org/10.1080/14728222.2021.1982896
Trubicka, J., Zemojtel, T., Hecht, J., Falana, K., Piekutowska- Abramczuk, D., Płoski, R., Perek-Polnik, M., Drogosiewicz, M., Grajkowska, W., Ciara, E., Moszczyńska, E., Dembowska-Bagińska, B., Perek, D., Chrzanowska, K. H., Krajewska-Walasek, M., & Lastowska, M. (2017). The germline variants in DNA repair genes in pediatric medulloblastoma: A challenge for current therapeutic strategies. BMC Cancer, 17(1), 1–11. https://doi.org/10.1186/s12885-017-3211-y
Zahraa F. Audi; Zahraa Saker; Mahdi Rizk; Hayat Harati; Youssef Fares; Hisham F. Bahmad; Sanaa M. Nabha; (2021). Immunosuppression in Medulloblastoma: Insights into Cancer Immunity and Immunotherapy. Current Treatment Options in Oncology, (), doi: 10.1007/s11864-021-00874-9
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