NRP1 como potencial alvo molecular para meduloblastoma
Barra lateral de artigos
Conteúdo do artigo principal
Resumo
Introdução: Meduloblastoma é tumor maligno, altamente agressivo e de rápido crescimento que surge no cerebelo ou no assoalho do quarto ventrículo e tronco cerebral, especialmente em crianças. Mesmo com avanços na terapia, a morbimortalidade permanece grande desafio. Por isso, novos tratamentos são necessários para reduzir esses desfechos.
Objetivo: Revisar a relação NRP1 (neuropilina 1) e meduloblastoma como potencial alvo terapêutico e, também, com sobrevida global.
Método: Trata-se de revisão narrativa realizada nas bases de dados PubMed e Scielo. A busca utilizou as seguintes palavras-chave: “neuropilinas, meduloblastoma, tumores cerebrais, pediatria”. Os critérios de inclusão foram artigos de revisão, estudos experimentais, pesquisas pré-clínicas e clínicas, em inglês e português, e disponíveis em texto completo. Os artigos selecionados foram analisados com base nas tecnologias abordadas, perspectivas futuras e desafios mencionados, doenças referidas e ideia central do artigo.
Resultado: Foram incluídos 30 artigos
Conclusão: Os meduloblastomas possuem altos níveis transcricionais de neuropilina (NRP1) e seus baixos níveis relacionam-se com menor sobrevida global, especialmente nos SHH. Nesse sentido, a NRP1 e seu complexo sistema de atuação aparece como potencial alvo de terapias oncológicas para tumores cerebrais.
Detalhes do artigo
Este trabalho está licenciado sob uma licença Creative Commons Attribution 4.0 International License.
Referências
Pollack IF. Brain tumors in children. N Engl J Med. 1994;331(22):1500-7. Doi: 10.1056/NEJM199412013312207
Schepke E, Tisell M, Kennedy C, Puget S, Ferroli P, Chevignard M, et al. Effects of the growth pattern of medulloblastoma on short-term neurological impairments after surgery: results from the prospective multicenter HIT-SIOP PNET 4 study. J Neurosurg Pediatr. 2020;17:1-9. Doi: 10.3171/2019.11.peds19349
Cho YJ, Tsherniak A, Tamayo P, Santagata S, Ligon A, Greulich H, et al. Integrative genomic analysis of medulloblastoma identifies a molecular subgroup that drives poor clinical outcome. J Clin Oncol. 2011;29(11):1424-30. Doi: 10.1200/jco.2010.28.5148
Matsuo S, Takahashi M, Inoue K, Tamura K, Irie K, Kodama Y, et al. Thickened area of external granular layer and Ki-67 positive focus are early events of medulloblastoma in Ptch1(+)/(-) mice. Exp Toxicol Pathol. 2013;65(6):863-73. Doi: 10.1016/j.etp.2012.12.005
Ning MS, Perkins SM, Dewees T, Shinohara ET. Evidence of high mortality in long term survivors of childhood medulloblastoma. J Neurooncol. 2015;122(2):321-7. Doi: 10.1007/s11060-014-1712-y
National Cancer Institute. Childhood Medulloblastoma and Other Central Nervous System Embryonal Tumors Treatment (PDQ®)–Health Professional Version. 2023. Disponível em: https://www.cancer.gov/types/brain/hp/child-cns-embryonal-treatment-pdq
Li KK, Lau KM, Ng HK. Signaling pathway and molecular subgroups of medulloblastoma. Int J Clin Exp Pathol. 2013;6(7):1211-22.
Gajjar A, Chintagumpala M, Ashley D, Kellie S, Kun LE, Merchant TE, et al. Risk-adapted craniospinal radiotherapy followed by high-dose chemotherapy and stem-cell rescue in children with newly diagnosed medulloblastoma (St Jude Medulloblastoma-96): long-term results from a prospective, multicentre trial. Lancet Oncol. 2006;7(10):813-20. Doi: 10.1016/s1470-2045(06)70867-1
Menyhart O, Gyorffy B. Molecular stratifications, biomarker candidates and new therapeutic options in current medulloblastoma treatment approaches. Cancer Metastasis Rev. 2020;39(1):211-33. Doi: 10.1007/s10555-020-09854-1
Louis DN, Perry A, Wesseling P, Brat DJ, Cree IA, Figarella-Branger D, et al. The 2021 WHO Classification of Tumors of the Central Nervous System: a summary. Neuro Oncol. 2021;23(8):1231-51. Doi: 10.1093%2Fneuonc%2Fnoab106
Quinlan A, Rizzolo D. Understanding medulloblastoma. JAAPA. 2017;30(10):30-6. Doi: 10.1097/01.jaa.0000524717.71084.50
Cavalli FMG, Remke M, Rampasek L, Peacock J, Shih DJH, Luu B, et al. Intertumoral Heterogeneity within Medulloblastoma Subgroups. Cancer Cell. 2017;31(6):737-54. Doi: 10.1016/j.ccell.2017.05.005
Dufour C, Beaugrand A, Pizer B, Micheli J, Aubelle MS, Fourcade A, et al. Metastatic Medulloblastoma in Childhood: Chang's Classification Revisited. Int J Surg Oncol. 2012;2012:245385. Doi: 10.1155/2012/245385
Chaudhary B, Khaled YS, Ammori BJ, Elkord E. Neuropilin 1: function and therapeutic potential in cancer. Cancer Immunol Immunother. 2014;63(2):81-99. Doi: 10.1007/s00262-013-1500-0
Pan Q, Chanthery Y, Liang WC, Stawicki S, Mak J, Rathore N, et al. Blocking neuropilin-1 function has an additive effect with anti-VEGF to inhibit tumor growth. Cancer Cell. 2007;11(1):53-67. Doi: 10.1016/j.ccr.2006.10.018
Vieira JM, Schwarz Q, Ruhrberg C. Selective requirements for NRP1 ligands during neurovascular patterning. Development. 2007;134(10):1833-43. Doi: 10.1242%2Fdev.002402
Eichmann A, Makinen T, Alitalo K. Neural guidance molecules regulate vascular remodeling and vessel navigation. Genes Dev. 2005;19(9):1013-21. Doi: 10.1101/gad.1305405
Kreuter M, Bielenberg D, Hida Y, Hida K, Klagsbrun M. Role of neuropilins and semaphorins in angiogenesis and cancer. Ann Hematol. 2002;81(Suppl 2):S74.
Roy S, Bag AK, Singh RK, Talmadge JE, Batra SK, Datta K. Multifaceted Role of Neuropilins in the Immune System: Potential Targets for Immunotherapy. Front Immunol. 2017;8:1228. Doi: 10.3389/fimmu.2017.01228
Douyere M, Chastagner P, Boura C. Neuropilin-1: A Key Protein to Consider in the Progression of Pediatric Brain Tumors. Front Oncol. 2021;11:665634. Doi: 10.3389%2Ffonc.2021.665634
Latil A, Bieche I, Pesche S, Valeri A, Fournier G, Cussenot O, et al. VEGF overexpression in clinically localized prostate tumors and neuropilin-1 overexpression in metastatic forms. Int J Cancer. 2000;89(2):167-71. Doi: 10.1002/(sici)1097-0215(20000320)89:2%3C167::aid-ijc11%3E3.0.co;2-9
Bachelder RE, Crago A, Chung J, Wendt MA, Shaw LM, Robinson G, et al. Vascular endothelial growth factor is an autocrine survival factor for neuropilin-expressing breast carcinoma cells. Cancer Res. 2001;61(15):5736-40.
Beierle EA, Dai W, Langham MR, Jr., Copeland EM, 3rd, Chen MK. Expression of VEGF receptors in cocultured neuroblastoma cells. J Surg Res. 2004;119(1):56-65. Doi: 10.1016/j.jss.2004.01.002
de Araújo MA, Malafaia O, Ribas-Filho JM, Fratini L, Roesler R, Isolan GR. Low Expression of the NRP1 Gene Is Associated with Shorter Overall Survival in Patients with Sonic Hedgehog and Group 3 Medulloblastoma. Int J Mol Sci. 2023;24(14):11601. Doi: 10.3390/ijms241411601
Zahnreich S, Schmidberger H. Childhood Cancer: Occurrence, Treatment and Risk of Second Primary Malignancies. Cancers (Basel). 2021;13(11):2607. Doi: 10.3390/cancers13112607
Solomon BD, Mueller C, Chae WJ, Alabanza LM, Bynoe MS. Neuropilin-1 attenuates autoreactivity in experimental autoimmune encephalomyelitis. Proc Natl Acad Sci U S A. 2011;108(5):2040-5. Doi: 10.1073/pnas.1008721108
Snuderl M, Batista A, Kirkpatrick ND, de Almodovar CR, Riedemann L, Walsh EC, et al. Targeting placental growth factor/neuropilin 1 pathway inhibits growth and spread of medulloblastoma. Cell. 2013;152(5):1065-76. Doi: 10.1016/j.cell.2013.01.036
Zhang G, Chen L, Sun K, Khan AA, Yan J, Liu H, et al. Neuropilin-1 (NRP-1)/GIPC1 pathway mediates glioma progression. Tumour Biol. 2016;37(10):13777-88. Doi: 10.1007/s13277-016-5138-3
Piechnik A, Dmoszynska A, Omiotek M, Mlak R, Kowal M, Stilgenbauer S, et al. The VEGF receptor, neuropilin-1, represents a promising novel target for chronic lymphocytic leukemia patients. Int J Cancer. 2013;133(6):1489-96. Doi: 10.1002/ijc.28135
Ishizuka Y, Koshinaga T, Hirano T, Nagasaki-Maeoka E, Watanabe Y, Hoshi R, et al. NRP1 knockdown promotes the migration and invasion of human neuroblastoma-derived SK‑N‑AS cells via the activation of beta1 integrin expression. Int J Oncol. 2018;53(1):159-66. Doi: 10.3892/ijo.2018.4397
Buffon VA, Conti BP, Beltrame CM, Sobral ACL, Simm EB, Bark SA. Perfil epidemiológico de tumores intracranianos metastáticos submetidos à neurocirurgia. BioSCIENCE. 2022;80(2): Doi: 100-5. 10.55684/80.2.23