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当代肿瘤药物靶点

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ISSN (Print): 1568-0096
ISSN (Online): 1873-5576

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Review Article

TrkB信号通路调控肿瘤致瘤性和转移的研究进展

卷 20, 期 10, 2020

页: [779 - 788] 页: 10

弟呕挨: 10.2174/1568009620999200730183631

价格: $65

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摘要

原肌球蛋白受体激酶(Trk) B Trkb是脑源性神经营养因子(BDNF)的特异性结合受体，支持多种人类恶性肿瘤的临床病理学。TrkB和TrkB融合蛋白在许多癌症患者中被观察到过表达。此外，这些蛋白已在多种类型的细胞中观察到。少数信号通路可被BDNF/TrkB通路的异常激活所调控。这些信号通路包括PI3K/Akt通路、EGFR的转活化、磷脂酶c -γ(PLCγ)通路、Ras-Raf-MEK-ERK通路、Jak/STAT通路、核因子kappalight-活化B细胞链增强子(NF-kB)通路。当BDNF/TrkB通路在肿瘤中过度表达时，与临床预后降低和患者生存时间缩短相关。靶向BDNF/TrkB通路，使用Trk抑制剂恩瑞替尼、拉罗瑞替尼等是肿瘤靶向治疗的有希望的方法。本文就TrkB通路在癌症发病机制中的作用及其作为潜在治疗靶点的价值作一综述。

关键词: TrkB，TrkB融合，TrkB抑制剂，体细胞突变，靶向治疗，致瘤性。

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[1]
Bibel, M.; Barde, Y.A. Neurotrophins: key regulators of cell fate and cell shape in the vertebrate nervous system. Genes Dev., 2000, 14(23), 2919-2937.
[http://dx.doi.org/10.1101/gad.841400] [PMID: 11114882]
[2]
Segal, R.A. Selectivity in neurotrophin signaling: theme and variations. Annu. Rev. Neurosci., 2003, 26, 299-330.
[http://dx.doi.org/10.1146/annurev.neuro.26.041002.131421] [PMID: 12598680]
[3]
Levi-Montalcini, R. The nerve growth factor 35 years later. Science, 1987, 237(4819), 1154-1162.
[http://dx.doi.org/10.1126/science.3306916] [PMID: 3306916]
[4]
Teng, K.K.; Felice, S.; Kim, T.; Hempstead, B.L. Understanding proneurotrophin actions: Recent advances and challenges. Dev. Neurobiol., 2010, 70(5), 350-359.
[http://dx.doi.org/10.1002/dneu.20768] [PMID: 20186707]
[5]
Al-Qudah, M.A.; Al-Dwairi, A. Mechanisms and regulation of neurotrophin synthesis and secretion. Neurosciences (Riyadh), 2016, 21(4), 306-313.
[6]
Thiele, C.J.; Li, Z.; McKee, A.E. On Trk--the TrkB signal transduction pathway is an increasingly important target in cancer biology. Clin. Cancer Res., 2009, 15(19), 5962-5967.
[http://dx.doi.org/10.1158/1078-0432.CCR-08-0651] [PMID: 19755385]
[7]
Reichardt, L.F. Neurotrophin-regulated signalling pathways. Philos. Trans. R. Soc. Lond. B Biol. Sci., 2006, 361(1473), 1545-1564.
[http://dx.doi.org/10.1098/rstb.2006.1894] [PMID: 16939974]
[8]
Salehi, A.; Verhaagen, J.; Dijkhuizen, P.A.; Swaab, D.F. Co-localization of high-affinity neurotrophin receptors in nucleus basalis of Meynert neurons and their differential reduction in Alzheimer’s disease. Neuroscience, 1996, 75(2), 373-387.
[http://dx.doi.org/10.1016/0306-4522(96)00273-4] [PMID: 8931004]
[9]
Ginsberg, S.D.; Che, S.; Wuu, J.; Counts, S.E.; Mufson, E.J. Down regulation of trk but not p75NTR gene expression in single cholinergic basal forebrain neurons mark the progression of Alzheimer’s disease. J. Neurochem., 2006, 97(2), 475-487.
[http://dx.doi.org/10.1111/j.1471-4159.2006.03764.x] [PMID: 16539663]
[10]
Huang, Y.; Huang, C.; Yun, W. Peripheral BDNF/TrkB protein expression is decreased in Parkinson’s disease but not in Essential tremor. J. Clin. Neurosci., 2019, 63, 176-181.
[http://dx.doi.org/10.1016/j.jocn.2019.01.017] [PMID: 30723034]
[11]
Bothwell, M. Recent advances in understanding context-dependent mechanisms controlling neurotrophin signaling and function. F1000 Res., 2019, 8, 8.
[http://dx.doi.org/10.12688/f1000research.19174.1] [PMID: 31583078]
[12]
Brodeur, G.M.; Nakagawara, A.; Yamashiro, D.J.; Ikegaki, N.; Liu, X.G.; Azar, C.G.; Lee, C.P.; Evans, A.E. Expression of TrkA, TrkB and TrkC in human neuroblastomas. J. Neurooncol., 1997, 31(1-2), 49-55.
[http://dx.doi.org/10.1023/A:1005729329526] [PMID: 9049830]
[13]
Cheung, N.K.; Dyer, M.A. Neuroblastoma: developmental biology, cancer genomics and immunotherapy. Nat. Rev. Cancer, 2013, 13(6), 397-411.
[http://dx.doi.org/10.1038/nrc3526] [PMID: 23702928]
[14]
Ho, R.; Eggert, A.; Hishiki, T.; Minturn, J.E.; Ikegaki, N.; Foster, P.; Camoratto, A.M.; Evans, A.E.; Brodeur, G.M. Resistance to chemotherapy mediated by TrkB in neuroblastomas. Cancer Res., 2002, 62(22), 6462-6466.
[PMID: 12438236]
[15]
Xiong, J.; Zhou, L.I.; Lim, Y.; Yang, M.; Zhu, Y.H.; Li, Z.W.; Fu, D.L.; Zhou, X.F. Mature brain-derived neurotrophic factor and its receptor TrkB are upregulated in human glioma tissues. Oncol. Lett., 2015, 10(1), 223-227.
[http://dx.doi.org/10.3892/ol.2015.3181] [PMID: 26171003]
[16]
Tajima, Y.; Molina, R.P., Jr; Rorke, L.B.; Kaplan, D.R.; Radeke, M.; Feinstein, S.C.; Lee, V.M.; Trojanowski, J.Q. Neurotrophins and neuronal versus glial differentiation in medulloblastomas and other pediatric brain tumors. Acta Neuropathol., 1998, 95(4), 325-332.
[http://dx.doi.org/10.1007/s004010050806] [PMID: 9560008]
[17]
Tanaka, K.; Shimura, T.; Kitajima, T.; Kondo, S.; Ide, S.; Okugawa, Y.; Saigusa, S.; Toiyama, Y.; Inoue, Y.; Araki, T.; Uchida, K.; Mohri, Y.; Kusunoki, M. Tropomyosin-related receptor kinase B at the invasive front and tumour cell dedifferentiation in gastric cancer. Br. J. Cancer, 2014, 110(12), 2923-2934.
[http://dx.doi.org/10.1038/bjc.2014.228] [PMID: 24853179]
[18]
Okugawa, Y.; Tanaka, K.; Inoue, Y.; Kawamura, M.; Kawamoto, A.; Hiro, J.; Saigusa, S.; Toiyama, Y.; Ohi, M.; Uchida, K.; Mohri, Y.; Kusunoki, M. Brain-derived neurotrophic factor/tropomyosin-related kinase B pathway in gastric cancer. Br. J. Cancer, 2013, 108(1), 121-130.
[http://dx.doi.org/10.1038/bjc.2012.499] [PMID: 23175149]
[19]
Choi, B.; Lee, E.J.; Shin, M.K.; Park, Y.S.; Ryu, M.H.; Kim, S.M.; Kim, E.Y.; Lee, H.K.; Chang, E.J. Upregulation of brain-derived neurotrophic factor in advanced gastric cancer contributes to bone metastatic osteolysis by inducing long pentraxin 3. Oncotarget, 2016, 7(34), 55506-55517.
[http://dx.doi.org/10.18632/oncotarget.10747] [PMID: 27458153]
[20]
Au, C.W.; Siu, M.K.; Liao, X.; Wong, E.S.; Ngan, H.Y.; Tam, K.F.; Chan, D.C.; Chan, Q.K.; Cheung, A.N. Tyrosine kinase B receptor and BDNF expression in ovarian cancers - Effect on cell migration, angiogenesis and clinical outcome. Cancer Lett., 2009, 281(2), 151-161.
[http://dx.doi.org/10.1016/j.canlet.2009.02.025] [PMID: 19307055]
[21]
Bao, W.; Qiu, H.; Yang, T.; Luo, X.; Zhang, H.; Wan, X. Upregulation of TrkB promotes epithelial-mesenchymal transition and anoikis resistance in endometrial carcinoma. PLoS One, 2013, 8(7), e70616.
[22]
Li, L.; Zhu, L. Expression and clinical significance of TrkB in sinonasal squamous cell carcinoma: a pilot study. Int. J. Oral Maxillofac. Surg., 2017, 46(2), 144-150.
[http://dx.doi.org/10.1016/j.ijom.2016.09.027] [PMID: 27810139]
[23]
Li, S.S.; Liu, J.J.; Wang, S.; Tang, Q.L.; Liu, B.B.; Yang, X.M. Clinical significance of TrkB expression in nasopharyngeal carcinoma. Oncol. Rep., 2014, 31(2), 665-672.
[http://dx.doi.org/10.3892/or.2013.2878] [PMID: 24297477]
[24]
Okamura, K.; Harada, T.; Wang, S.; Ijichi, K.; Furuyama, K.; Koga, T.; Okamoto, T.; Takayama, K.; Yano, T.; Nakanishi, Y. Expression of TrkB and BDNF is associated with poor prognosis in non-small cell lung cancer. Lung Cancer, 2012, 78(1), 100-106.
[http://dx.doi.org/10.1016/j.lungcan.2012.07.011] [PMID: 22906736]
[25]
Kimura, S.; Harada, T.; Ijichi, K.; Tanaka, K.; Liu, R.; Shibahara, D.; Kawano, Y.; Otsubo, K.; Yoneshima, Y.; Iwama, E.; Nakanishi, Y.; Okamoto, I. Expression of brain-derived neurotrophic factor and its receptor TrkB is associated with poor prognosis and a malignant phenotype in small cell lung cancer. Lung Cancer, 2018, 120, 98-107.
[http://dx.doi.org/10.1016/j.lungcan.2018.04.005] [PMID: 29748024]
[26]
Llovet, J.M.; Montal, R.; Sia, D.; Finn, R.S. Molecular therapies and precision medicine for hepatocellular carcinoma. Nat. Rev. Clin. Oncol., 2018, 15(10), 599-616.
[http://dx.doi.org/10.1038/s41571-018-0073-4] [PMID: 30061739]
[27]
Lam, C.T.; Yang, Z.F.; Lau, C.K.; Tam, K.H.; Fan, S.T.; Poon, R.T. Brain-derived neurotrophic factor promotes tumorigenesis via induction of neovascularization: implication in hepatocellular carcinoma. Clin. Cancer Res., 2011, 17(10), 3123-3133.
[http://dx.doi.org/10.1158/1078-0432.CCR-10-2802] [PMID: 21421859]
[28]
Fan, M.; Sun, J.; Wang, W.; Fan, J.; Wang, L.; Zhang, X.; Yang, A.; Wang, W.; Zhang, R.; Li, J. Tropomyosin-related kinase B promotes distant metastasis of colorectal cancer through protein kinase B-mediated anoikis suppression and correlates with poor prognosis. Apoptosis, 2014, 19(5), 860-870.
[http://dx.doi.org/10.1007/s10495-014-0968-1] [PMID: 24549576]
[29]
Smirnova, L.; Gräfe, A.; Seiler, A.; Schumacher, S.; Nitsch, R.; Wulczyn, F.G. Regulation of miRNA expression during neural cell specification. Eur. J. Neurosci., 2005, 21(6), 1469-1477.
[http://dx.doi.org/10.1111/j.1460-9568.2005.03978.x] [PMID: 15845075]
[30]
Miska, E.A.; Alvarez-Saavedra, E.; Townsend, M.; Yoshii, A.; Sestan, N.; Rakic, P.; Constantine-Paton, M.; Horvitz, H.R. Microarray analysis of microRNA expression in the developing mammalian brain. Genome Biol., 2004, 5(9), R68.
[http://dx.doi.org/10.1186/gb-2004-5-9-r68] [PMID: 15345052]
[31]
Bartel, D.P. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell, 2004, 116(2), 281-297.
[http://dx.doi.org/10.1016/S0092-8674(04)00045-5] [PMID: 14744438]
[32]
Stoilov, P.; Castren, E.; Stamm, S. Analysis of the human TrkB gene genomic organization reveals novel TrkB isoforms, unusual gene length, and splicing mechanism. Biochem. Biophys. Res. Commun., 2002, 290(3), 1054-1065.
[http://dx.doi.org/10.1006/bbrc.2001.6301] [PMID: 11798182]
[33]
Wong, J. Regulation of a TrkB Alternative Transcript by microRNAs. Dement. Geriatr. Cogn. Disord. Extra, 2014, 4(3), 364-374.
[http://dx.doi.org/10.1159/000365917] [PMID: 25337079]
[34]
Bao, W.; Wang, H.H.; Tian, F.J.; He, X.Y.; Qiu, M.T.; Wang, J.Y.; Zhang, H.J.; Wang, L.H.; Wan, X.P. A TrkB-STAT3-miR-204-5p regulatory circuitry controls proliferation and invasion of endometrial carcinoma cells. Mol. Cancer, 2013, 12, 155.
[http://dx.doi.org/10.1186/1476-4598-12-155] [PMID: 24321270]
[35]
Rose, C.R.; Blum, R.; Pichler, B.; Lepier, A.; Kafitz, K.W.; Konnerth, A. Truncated TrkB-T1 mediates neurotrophin-evoked calcium signalling in glia cells. Nature, 2003, 426(6962), 74-78.
[http://dx.doi.org/10.1038/nature01983] [PMID: 14603320]
[36]
Maussion, G.; Yang, J.; Yerko, V.; Barker, P.; Mechawar, N.; Ernst, C.; Turecki, G. Regulation of a truncated form of tropomyosin-related kinase B (TrkB) by Hsa-miR-185* in frontal cortex of suicide completers. PLoS One, 2012, 7(6), e39301.
[37]
Cochrane, D.R.; Howe, E.N.; Spoelstra, N.S.; Richer, J.K. Loss of miR-200c: A Marker of Aggressiveness and Chemoresistance in Female Reproductive Cancers. J. Oncol., 2010, 2010821717.
[38]
Kopp, F.; Oak, P.S.; Wagner, E.; Roidl, A. miR-200c sensitizes breast cancer cells to doxorubicin treatment by decreasing TrkB and Bmi1 expression. PLoS One, 2012, 7(11), e50469.
[39]
Howe, E.N.; Cochrane, D.R.; Cittelly, D.M.; Richer, J.K. miR-200c targets a NF-κB up-regulated TrkB/NTF3 autocrine signaling loop to enhance anoikis sensitivity in triple negative breast cancer. PLoS One, 2012, 7(11), e49987.
[40]
Stratton, M.R.; Campbell, P.J.; Futreal, P.A. The cancer genome. Nature, 2009, 458(7239), 719-724.
[http://dx.doi.org/10.1038/nature07943] [PMID: 19360079]
[41]
Hanahan, D.; Weinberg, R.A. The hallmarks of cancer. Cell, 2000, 100(1), 57-70.
[http://dx.doi.org/10.1016/S0092-8674(00)81683-9] [PMID: 10647931]
[42]
Bardelli, A.; Parsons, D.W.; Silliman, N.; Ptak, J.; Szabo, S.; Saha, S.; Markowitz, S.; Willson, J.K.; Parmigiani, G.; Kinzler, K.W.; Vogelstein, B.; Velculescu, V.E. Mutational analysis of the tyrosine kinome in colorectal cancers. Science, 2003, 300(5621), 949.
[43]
Deihimi, S.; Lev, A.; Slifker, M.; Shagisultanova, E.; Xu, Q.; Jung, K.; Vijayvergia, N.; Ross, E.A.; Xiu, J.; Swensen, J.; Gatalica, Z.; Andrake, M.; Dunbrack, R.L.; El-Deiry, W.S. BRCA2, EGFR, and NTRK mutations in mismatch repair-deficient colorectal cancers with MSH2 or MLH1 mutations. Oncotarget, 2017, 8(25), 39945-39962.
[http://dx.doi.org/10.18632/oncotarget.18098] [PMID: 28591715]
[44]
Davies, H.; Hunter, C.; Smith, R.; Stephens, P.; Greenman, C.; Bignell, G.; Teague, J.; Butler, A.; Edkins, S.; Stevens, C.; Parker, A.; O’Meara, S.; Avis, T.; Barthorpe, S.; Brackenbury, L.; Buck, G.; Clements, J.; Cole, J.; Dicks, E.; Edwards, K.; Forbes, S.; Gorton, M.; Gray, K.; Halliday, K.; Harrison, R.; Hills, K.; Hinton, J.; Jones, D.; Kosmidou, V.; Laman, R.; Lugg, R.; Menzies, A.; Perry, J.; Petty, R.; Raine, K.; Shepherd, R.; Small, A.; Solomon, H.; Stephens, Y.; Tofts, C.; Varian, J.; Webb, A.; West, S.; Widaa, S.; Yates, A.; Brasseur, F.; Cooper, C.S.; Flanagan, A.M.; Green, A.; Knowles, M.; Leung, S.Y.; Looijenga, L.H.; Malkowicz, B.; Pierotti, M.A.; Teh, B.T.; Yuen, S.T.; Lakhani, S.R.; Easton, D.F.; Weber, B.L.; Goldstraw, P.; Nicholson, A.G.; Wooster, R.; Stratton, M.R.; Futreal, P.A. Somatic mutations of the protein kinase gene family in human lung cancer. Cancer Res., 2005, 65(17), 7591-7595.
[http://dx.doi.org/10.1158/0008-5472.CAN-05-1855] [PMID: 16140923]
[45]
Geiger, T.R.; Song, J.Y.; Rosado, A.; Peeper, D.S. Functional characterization of human cancer-derived TRKB mutations. PLoS One, 2011, 6(2), e16871.
[http://dx.doi.org/10.1371/journal.pone.0016871] [PMID: 21379385]
[46]
Rudd, M.L.; Mohamed, H.; Price, J.C.; O’Hara, A.J.; Le Gallo, M.; Urick, M.E.; Cruz, P.; Zhang, S.; Hansen, N.F.; Godwin, A.K.; Sgroi, D.C.; Wolfsberg, T.G.; Mullikin, J.C.; Merino, M.J.; Bell, D.W.; Bell, D.W. NISC Comparative Sequencing Program. Mutational analysis of the tyrosine kinome in serous and clear cell endometrial cancer uncovers rare somatic mutations in TNK2 and DDR1. BMC Cancer, 2014, 14, 884.
[http://dx.doi.org/10.1186/1471-2407-14-884] [PMID: 25427824]
[47]
Amatu, A.; Sartore-Bianchi, A.; Siena, S. NTRK gene fusions as novel targets of cancer therapy across multiple tumour types. ESMO Open, 2016, 1(2), e000023.
[48]
Nakagawara, A.; Liu, X.G.; Ikegaki, N.; White, P.S.; Yamashiro, D.J.; Nycum, L.M.; Biegel, J.A.; Brodeur, G.M. Cloning and chromosomal localization of the human TRK-B tyrosine kinase receptor gene (NTRK2). Genomics, 1995, 25(2), 538-546.
[http://dx.doi.org/10.1016/0888-7543(95)80055-Q] [PMID: 7789988]
[49]
Yeo, G.S.; Connie Hung, C.C.; Rochford, J.; Keogh, J.; Gray, J.; Sivaramakrishnan, S.; O’Rahilly, S.; Farooqi, I.S. A de novo mutation affecting human TrkB associated with severe obesity and developmental delay. Nat. Neurosci., 2004, 7(11), 1187-1189.
[http://dx.doi.org/10.1038/nn1336] [PMID: 15494731]
[50]
Qaddoumi, I.; Orisme, W.; Wen, J.; Santiago, T.; Gupta, K.; Dalton, J.D.; Tang, B.; Haupfear, K.; Punchihewa, C.; Easton, J.; Mulder, H.; Boggs, K.; Shao, Y.; Rusch, M.; Becksfort, J.; Gupta, P.; Wang, S.; Lee, R.P.; Brat, D.; Peter Collins, V.; Dahiya, S.; George, D.; Konomos, W.; Kurian, K.M.; McFadden, K.; Serafini, L.N.; Nickols, H.; Perry, A.; Shurtleff, S.; Gajjar, A.; Boop, F.A.; Klimo, P.D., Jr; Mardis, E.R.; Wilson, R.K.; Baker, S.J.; Zhang, J.; Wu, G.; Downing, J.R.; Tatevossian, R.G.; Ellison, D.W. Genetic alterations in uncommon low-grade neuroepithelial tumors: BRAF, FGFR1, and MYB mutations occur at high frequency and align with morphology. Acta Neuropathol., 2016, 131(6), 833-845.
[http://dx.doi.org/10.1007/s00401-016-1539-z] [PMID: 26810070]
[51]
Zhang, J.; Wu, G.; Miller, C.P.; Tatevossian, R.G.; Dalton, J.D.; Tang, B.; Orisme, W.; Punchihewa, C.; Parker, M.; Qaddoumi, I.; Boop, F.A.; Lu, C.; Kandoth, C.; Ding, L.; Lee, R.; Huether, R.; Chen, X.; Hedlund, E.; Nagahawatte, P.; Rusch, M.; Boggs, K.; Cheng, J.; Becksfort, J.; Ma, J.; Song, G.; Li, Y.; Wei, L.; Wang, J.; Shurtleff, S.; Easton, J.; Zhao, D.; Fulton, R.S.; Fulton, L.L.; Dooling, D.J.; Vadodaria, B.; Mulder, H.L.; Tang, C.; Ochoa, K.; Mullighan, C.G.; Gajjar, A.; Kriwacki, R.; Sheer, D.; Gilbertson, R.J.; Mardis, E.R.; Wilson, R.K.; Downing, J.R.; Baker, S.J.; Ellison, D.W.St. Jude Children’s Research Hospital–Washington University Pediatric Cancer Genome Project. Whole-genome sequencing identifies genetic alterations in pediatric low-grade gliomas. Nat. Genet., 2013, 45(6), 602-612.
[http://dx.doi.org/10.1038/ng.2611] [PMID: 23583981]
[52]
Jones, D.T.; Hutter, B.; Jäger, N.; Korshunov, A.; Kool, M.; Warnatz, H.J.; Zichner, T.; Lambert, S.R.; Ryzhova, M.; Quang, D.A.; Fontebasso, A.M.; Stütz, A.M.; Hutter, S.; Zuckermann, M.; Sturm, D.; Gronych, J.; Lasitschka, B.; Schmidt, S.; Seker-Cin, H.; Witt, H.; Sultan, M.; Ralser, M.; Northcott, P.A.; Hovestadt, V.; Bender, S.; Pfaff, E.; Stark, S.; Faury, D.; Schwartzentruber, J.; Majewski, J.; Weber, U.D.; Zapatka, M.; Raeder, B.; Schlesner, M.; Worth, C.L.; Bartholomae, C.C.; von Kalle, C.; Imbusch, C.D.; Radomski, S.; Lawerenz, C.; van Sluis, P.; Koster, J.; Volckmann, R.; Versteeg, R.; Lehrach, H.; Monoranu, C.; Winkler, B.; Unterberg, A.; Herold-Mende, C.; Milde, T.; Kulozik, A.E.; Ebinger, M.; Schuhmann, M.U.; Cho, Y.J.; Pomeroy, S.L.; von Deimling, A.; Witt, O.; Taylor, M.D.; Wolf, S.; Karajannis, M.A.; Eberhart, C.G.; Scheurlen, W.; Hasselblatt, M.; Ligon, K.L.; Kieran, M.W.; Korbel, J.O.; Yaspo, M.L.; Brors, B.; Felsberg, J.; Reifenberger, G.; Collins, V.P.; Jabado, N.; Eils, R.; Lichter, P.; Pfister, S.M. International Cancer Genome Consortium PedBrain Tumor Project. Recurrent somatic alterations of FGFR1 and NTRK2 in pilocytic astrocytoma. Nat. Genet., 2013, 45(8), 927-932.
[http://dx.doi.org/10.1038/ng.2682] [PMID: 23817572]
[53]
Wu, G.; Diaz, A.K.; Paugh, B.S.; Rankin, S.L.; Ju, B.; Li, Y.; Zhu, X.; Qu, C.; Chen, X.; Zhang, J.; Easton, J.; Edmonson, M.; Ma, X.; Lu, C.; Nagahawatte, P.; Hedlund, E.; Rusch, M.; Pounds, S.; Lin, T.; Onar-Thomas, A.; Huether, R.; Kriwacki, R.; Parker, M.; Gupta, P.; Becksfort, J.; Wei, L.; Mulder, H.L.; Boggs, K.; Vadodaria, B.; Yergeau, D.; Russell, J.C.; Ochoa, K.; Fulton, R.S.; Fulton, L.L.; Jones, C.; Boop, F.A.; Broniscer, A.; Wetmore, C.; Gajjar, A.; Ding, L.; Mardis, E.R.; Wilson, R.K.; Taylor, M.R.; Downing, J.R.; Ellison, D.W.; Zhang, J.; Baker, S.J. The genomic landscape of diffuse intrinsic pontine glioma and pediatric non-brainstem high-grade glioma. Nat. Genet., 2014, 46(5), 444-450.
[54]
Frattini, V.; Trifonov, V.; Chan, J.M.; Castano, A.; Lia, M.; Abate, F.; Keir, S.T.; Ji, A.X.; Zoppoli, P.; Niola, F.; Danussi, C.; Dolgalev, I.; Porrati, P.; Pellegatta, S.; Heguy, A.; Gupta, G.; Pisapia, D.J.; Canoll, P.; Bruce, J.N.; McLendon, R.E.; Yan, H.; Aldape, K.; Finocchiaro, G.; Mikkelsen, T.; Privé, G.G.; Bigner, D.D.; Lasorella, A.; Rabadan, R.; Iavarone, A. The integrated landscape of driver genomic alterations in glioblastoma. Nat. Genet., 2013, 45(10), 1141-1149.
[http://dx.doi.org/10.1038/ng.2734] [PMID: 23917401]
[55]
Stransky, N.; Cerami, E.; Schalm, S.; Kim, J.L.; Lengauer, C. The landscape of kinase fusions in cancer. Nat. Commun., 2014, 5, 4846.
[http://dx.doi.org/10.1038/ncomms5846] [PMID: 25204415]
[56]
Pattwell, S.S.; Konnick, E.Q.; Liu, Y.J.; Yoda, R.A.; Sekhar, L.N.; Cimino, P.J. Neurotrophic Receptor Tyrosine Kinase 2 (NTRK2) Alterations in Low-Grade Gliomas: Report of a Novel Gene Fusion Partner in a Pilocytic Astrocytoma and Review of the Literature. Case Rep. Pathol., 2020, 20205903863.
[57]
López, G.Y.; Perry, A.; Harding, B.; Li, M.; Santi, M. CDKN2A/B Loss Is Associated with Anaplastic Transformation in a Case of NTRK2 Fusion-positive Pilocytic Astrocytoma. Neuropathol. Appl. Neurobiol., 2019, 45(2), 174-178.
[http://dx.doi.org/10.1111/nan.12503] [PMID: 29804288]
[58]
Jones, K.A.; Bossler, A.D.; Bellizzi, A.M.; Snow, A.N. BCR-NTRK2 fusion in a low-grade glioma with distinctive morphology and unexpected aggressive behavior. Cold Spring Harb. Mol. Case Stud., 2019, 5(2), a003855.
[59]
Prabhakaran, N.; Guzman, M.A.; Navalkele, P.; Chow-Maneval, E.; Batanian, J.R. Novel TLE4-NTRK2 fusion in a ganglioglioma identified by array-CGH and confirmed by NGS: Potential for a gene targeted therapy. Neuropathology, 2018, 38(4), 380-386.
[http://dx.doi.org/10.1111/neup.12458] [PMID: 29502353]
[60]
Yuan, Y.; Ye, H.Q.; Ren, Q.C. Upregulation of the BDNF/TrKB pathway promotes epithelial-mesenchymal transition, as well as the migration and invasion of cervical cancer. Int. J. Oncol., 2018, 52(2), 461-472.
[PMID: 29345295]
[61]
Cai, Y.; Dodhia, S.; Su, G.H. Dysregulations in the PI3K pathway and targeted therapies for head and neck squamous cell carcinoma. Oncotarget, 2017, 8(13), 22203-22217.
[http://dx.doi.org/10.18632/oncotarget.14729] [PMID: 28108737]
[62]
Pause due in home health expansions as Congress reassesses? Nurs. Health Care, 1989, 10(6), 296-297.
[PMID: 2660016]
[63]
Wang, M.; Zhou, W.; Zhou, X.; Zhuang, F.; Chen, Q.; Li, M.; Ma, T.; Gu, S. Antidepressant-like effects of alarin produced by activation of TrkB receptor signaling pathways in chronic stress mice. Behav. Brain Res., 2015, 280, 128-140.
[http://dx.doi.org/10.1016/j.bbr.2014.11.039] [PMID: 25476565]
[64]
Summy, J.M.; Gallick, G.E. Src family kinases in tumor progression and metastasis. Cancer Metastasis Rev., 2003, 22(4), 337-358.
[http://dx.doi.org/10.1023/A:1023772912750] [PMID: 12884910]
[65]
Jiang, L.; Wang, Z.; Liu, C.; Gong, Z.; Yang, Y.; Kang, H.; Li, Y.; Hu, G. TrkB promotes laryngeal cancer metastasis via activation PI3K/AKT pathway. Oncotarget, 2017, 8(65), 108726-108737.
[http://dx.doi.org/10.18632/oncotarget.21711] [PMID: 29312563]
[66]
Kim, M.S.; Lee, W.S.; Jeong, J.; Kim, S.J.; Jin, W. Induction of metastatic potential by TrkB via activation of IL6/JAK2/STAT3 and PI3K/AKT signaling in breast cancer. Oncotarget, 2015, 6(37), 40158-40171.
[http://dx.doi.org/10.18632/oncotarget.5522] [PMID: 26515594]
[67]
Hua, Z.; Gu, X.; Dong, Y.; Tan, F.; Liu, Z.; Thiele, C.J.; Li, Z. PI3K and MAPK pathways mediate the BDNF/TrkB-increased metastasis in neuroblastoma. Tumour Biol., 2016.
[http://dx.doi.org/10.1007/s13277-016-5433-z] [PMID: 27752996]
[68]
Li, Z.; Oh, D.Y.; Nakamura, K.; Thiele, C.J. Perifosine-induced inhibition of Akt attenuates brain-derived neurotrophic factor/TrkB-induced chemoresistance in neuroblastoma in vivo. Cancer, 2011, 117(23), 5412-5422.
[http://dx.doi.org/10.1002/cncr.26133] [PMID: 21590687]
[69]
Iyer, R.; Varela, C.R.; Minturn, J.E.; Ho, R.; Simpson, A.M.; Light, J.E.; Evans, A.E.; Zhao, H.; Thress, K.; Brown, J.L.; Brodeur, G.M. AZ64 inhibits TrkB and enhances the efficacy of chemotherapy and local radiation in neuroblastoma xenografts. Cancer Chemother. Pharmacol., 2012, 70(3), 477-486.
[http://dx.doi.org/10.1007/s00280-012-1879-x] [PMID: 22623209]
[70]
Puehringer, D.; Orel, N.; Lüningschrör, P.; Subramanian, N.; Herrmann, T.; Chao, M.V.; Sendtner, M. EGF transactivation of Trk receptors regulates the migration of newborn cortical neurons. Nat. Neurosci., 2013, 16(4), 407-415.
[http://dx.doi.org/10.1038/nn.3333] [PMID: 23416450]
[71]
Götz, R.; Sendtner, M. Cooperation of tyrosine kinase receptor TrkB and epidermal growth factor receptor signaling enhances migration and dispersal of lung tumor cells. PLoS One, 2014, 9(6), e100944.
[72]
Qiu, L.; Zhou, C.; Sun, Y.; Di, W.; Scheffler, E.; Healey, S.; Kouttab, N.; Chu, W.; Wan, Y. Crosstalk between EGFR and TrkB enhances ovarian cancer cell migration and proliferation. Int. J. Oncol., 2006, 29(4), 1003-1011.
[http://dx.doi.org/10.3892/ijo.29.4.1003] [PMID: 16964397]
[73]
Siu, M.K.; Wong, O.G.; Cheung, A.N. TrkB as a therapeutic target for ovarian cancer. Expert Opin. Ther. Targets, 2009, 13(10), 1169-1178.
[74]
Lin, C.Y.; Chen, H.J.; Li, T.M.; Fong, Y.C.; Liu, S.C.; Chen, P.C.; Tang, C.H. β5 integrin up-regulation in brain-derived neurotrophic factor promotes cell motility in human chondrosarcoma. PLoS One, 2013, 8(7), e67990.
[75]
Drilon, A.; Li, G.; Dogan, S.; Gounder, M.; Shen, R.; Arcila, M.; Wang, L.; Hyman, D.M.; Hechtman, J.; Wei, G.; Cam, N.R.; Christiansen, J.; Luo, D.; Maneval, E.C.; Bauer, T.; Patel, M.; Liu, S.V.; Ou, S.H.; Farago, A.; Shaw, A.; Shoemaker, R.F.; Lim, J.; Hornby, Z.; Multani, P.; Ladanyi, M.; Berger, M.; Katabi, N.; Ghossein, R.; Ho, A.L. What hides behind the MASC: clinical response and acquired resistance to entrectinib after ETV6-NTRK3 identification in a mammary analogue secretory carcinoma (MASC). Ann. Oncol., 2016, 27(5), 920-926.
[http://dx.doi.org/10.1093/annonc/mdw042] [PMID: 26884591]
[76]
Russo, M.; Misale, S.; Wei, G.; Siravegna, G.; Crisafulli, G.; Lazzari, L.; Corti, G.; Rospo, G.; Novara, L.; Mussolin, B.; Bartolini, A.; Cam, N.; Patel, R.; Yan, S.; Shoemaker, R.; Wild, R.; Di Nicolantonio, F.; Bianchi, A.S.; Li, G.; Siena, S.; Bardelli, A. Acquired Resistance to the TRK Inhibitor Entrectinib in Colorectal Cancer. Cancer Discov., 2016, 6(1), 36-44.
[http://dx.doi.org/10.1158/2159-8290.CD-15-0940] [PMID: 26546295]
[77]
Doebele, R.C.; Davis, L.E.; Vaishnavi, A.; Le, A.T.; Estrada-Bernal, A.; Keysar, S.; Jimeno, A.; Varella-Garcia, M.; Aisner, D.L.; Li, Y.; Stephens, P.J.; Morosini, D.; Tuch, B.B.; Fernandes, M.; Nanda, N.; Low, J.A. An Oncogenic NTRK Fusion in a Patient with Soft-Tissue Sarcoma with Response to the Tropomyosin-Related Kinase Inhibitor LOXO-101. Cancer Discov., 2015, 5(10), 1049-1057.
[http://dx.doi.org/10.1158/2159-8290.CD-15-0443] [PMID: 26216294]
[78]
Drilon, A.; Siena, S.; Ou, S.I.; Patel, M.; Ahn, M.J.; Lee, J.; Bauer, T.M.; Farago, A.F.; Wheler, J.J.; Liu, S.V.; Doebele, R.; Giannetta, L.; Cerea, G.; Marrapese, G.; Schirru, M.; Amatu, A.; Bencardino, K.; Palmeri, L.; Sartore-Bianchi, A.; Vanzulli, A.; Cresta, S.; Damian, S.; Duca, M.; Ardini, E.; Li, G.; Christiansen, J.; Kowalski, K.; Johnson, A.D.; Patel, R.; Luo, D.; Chow-Maneval, E.; Hornby, Z.; Multani, P.S.; Shaw, A.T.; De Braud, F.G. Safety and Antitumor Activity of the Multitargeted Pan-TRK, ROS1, and ALK Inhibitor Entrectinib: Combined Results from Two Phase I Trials (ALKA-372-001 and STARTRK-1). Cancer Discov., 2017, 7(4), 400-409.
[http://dx.doi.org/10.1158/2159-8290.CD-16-1237] [PMID: 28183697]
[79]
Iyer, R.; Wehrmann, L.; Golden, R.L.; Naraparaju, K.; Croucher, J.L.; MacFarland, S.P.; Guan, P.; Kolla, V.; Wei, G.; Cam, N.; Li, G.; Hornby, Z.; Brodeur, G.M. Entrectinib is a potent inhibitor of Trk-driven neuroblastomas in a xenograft mouse model. Cancer Lett., 2016, 372(2), 179-186.
[80]
Rolfo, C.; Ruiz, R.; Giovannetti, E.; Gil-Bazo, I.; Russo, A.; Passiglia, F.; Giallombardo, M.; Peeters, M.; Raez, L. Entrectinib: a potent new TRK, ROS1, and ALK inhibitor. Expert Opin. Investig. Drugs, 2015, 24(11), 1493-1500.
[http://dx.doi.org/10.1517/13543784.2015.1096344] [PMID: 26457764]
[81]
Ardini, E.; Menichincheri, M.; Banfi, P.; Bosotti, R.; De Ponti, C.; Pulci, R.; Ballinari, D.; Ciomei, M.; Texido, G.; Degrassi, A.; Avanzi, N.; Amboldi, N.; Saccardo, M.B.; Casero, D.; Orsini, P.; Bandiera, T.; Mologni, L.; Anderson, D.; Wei, G.; Harris, J.; Vernier, J.M.; Li, G.; Felder, E.; Donati, D.; Isacchi, A.; Pesenti, E.; Magnaghi, P.; Galvani, A. Entrectinib, a Pan-TRK, ROS1, and ALK Inhibitor with Activity in Multiple Molecularly Defined Cancer Indications. Mol. Cancer Ther., 2016, 15(4), 628-639.
[http://dx.doi.org/10.1158/1535-7163.MCT-15-0758] [PMID: 26939704]
[82]
Menichincheri, M.; Ardini, E.; Magnaghi, P.; Avanzi, N.; Banfi, P.; Bossi, R.; Buffa, L.; Canevari, G.; Ceriani, L.; Colombo, M.; Corti, L.; Donati, D.; Fasolini, M.; Felder, E.; Fiorelli, C.; Fiorentini, F.; Galvani, A.; Isacchi, A.; Borgia, A.L.; Marchionni, C.; Nesi, M.; Orrenius, C.; Panzeri, A.; Pesenti, E.; Rusconi, L.; Saccardo, M.B.; Vanotti, E.; Perrone, E.; Orsini, P. Discovery of Entrectinib: A New 3-Aminoindazole As a Potent Anaplastic Lymphoma Kinase (ALK), c-ros Oncogene 1 Kinase (ROS1), and Pan-Tropomyosin Receptor Kinases (Pan-TRKs) inhibitor. J. Med. Chem., 2016, 59(7), 3392-3408.
[http://dx.doi.org/10.1021/acs.jmedchem.6b00064] [PMID: 27003761]
[83]
Drilon, A.; Laetsch, T.W.; Kummar, S.; DuBois, S.G.; Lassen, U.N.; Demetri, G.D.; Nathenson, M.; Doebele, R.C.; Farago, A.F.; Pappo, A.S.; Turpin, B.; Dowlati, A.; Brose, M.S.; Mascarenhas, L.; Federman, N.; Berlin, J.; El-Deiry, W.S.; Baik, C.; Deeken, J.; Boni, V.; Nagasubramanian, R.; Taylor, M.; Rudzinski, E.R.; Meric-Bernstam, F.; Sohal, D.P.S.; Ma, P.C.; Raez, L.E.; Hechtman, J.F.; Benayed, R.; Ladanyi, M.; Tuch, B.B.; Ebata, K.; Cruickshank, S.; Ku, N.C.; Cox, M.C.; Hawkins, D.S.; Hong, D.S.; Hyman, D.M. Efficacy of Larotrectinib in TRK Fusion-Positive Cancers in Adults and Children. N. Engl. J. Med., 2018, 378(8), 731-739.
[http://dx.doi.org/10.1056/NEJMoa1714448] [PMID: 29466156]
[84]
Scott, L.J. Larotrectinib: First Global Approval. Drugs, 2019, 79(2), 201-206.
[http://dx.doi.org/10.1007/s40265-018-1044-x] [PMID: 30635837]
[85]
Laetsch, T.W.; DuBois, S.G.; Mascarenhas, L.; Turpin, B.; Federman, N.; Albert, C.M.; Nagasubramanian, R.; Davis, J.L.; Rudzinski, E.; Feraco, A.M.; Tuch, B.B.; Ebata, K.T.; Reynolds, M.; Smith, S.; Cruickshank, S.; Cox, M.C.; Pappo, A.S.; Hawkins, D.S. Larotrectinib for paediatric solid tumours harbouring NTRK gene fusions: phase 1 results from a multicentre, open-label, phase 1/2 study. Lancet Oncol., 2018, 19(5), 705-714.
[http://dx.doi.org/10.1016/S1470-2045(18)30119-0] [PMID: 29606586]
[86]
Bowles, D.W.; Kessler, E.R.; Jimeno, A. Multi-targeted tyrosine kinase inhibitors in clinical development: focus on XL-184 (cabozantinib). Drugs Today (Barc), 2011, 47(11), 857-868.
[http://dx.doi.org/10.1358/dot.2011.47.11.1688487] [PMID: 22146228]
[87]
Zou, H.Y.; Li, Q.; Lee, J.H.; Arango, M.E.; McDonnell, S.R.; Yamazaki, S.; Koudriakova, T.B.; Alton, G.; Cui, J.J.; Kung, P.P.; Nambu, M.D.; Los, G.; Bender, S.L.; Mroczkowski, B.; Christensen, J.G. An orally available small-molecule inhibitor of c-Met, PF-2341066, exhibits cytoreductive antitumor efficacy through antiproliferative and antiangiogenic mechanisms. Cancer Res., 2007, 67(9), 4408-4417.
[http://dx.doi.org/10.1158/0008-5472.CAN-06-4443] [PMID: 17483355]
[88]
Cui, J.J.; Tran-Dubé, M.; Shen, H.; Nambu, M.; Kung, P.P.; Pairish, M.; Jia, L.; Meng, J.; Funk, L.; Botrous, I.; McTigue, M.; Grodsky, N.; Ryan, K.; Padrique, E.; Alton, G.; Timofeevski, S.; Yamazaki, S.; Li, Q.; Zou, H.; Christensen, J.; Mroczkowski, B.; Bender, S.; Kania, R.S.; Edwards, M.P. Structure based drug design of crizotinib (PF-02341066), a potent and selective dual inhibitor of mesenchymal-epithelial transition factor (c-MET) kinase and anaplastic lymphoma kinase (ALK). J. Med. Chem., 2011, 54(18), 6342-6363.
[http://dx.doi.org/10.1021/jm2007613] [PMID: 21812414]
[89]
Bergethon, K.; Shaw, A.T.; Ou, S.H.; Katayama, R.; Lovly, C.M.; McDonald, N.T.; Massion, P.P.; Siwak-Tapp, C.; Gonzalez, A.; Fang, R.; Mark, E.J.; Batten, J.M.; Chen, H.; Wilner, K.D.; Kwak, E.L.; Clark, J.W.; Carbone, D.P.; Ji, H.; Engelman, J.A.; Mino-Kenudson, M.; Pao, W.; Iafrate, A.J. ROS1 rearrangements define a unique molecular class of lung cancers. J. Clin. Oncol., 2012, 30(8), 863-870.
[http://dx.doi.org/10.1200/JCO.2011.35.6345] [PMID: 22215748]
[90]
Fuse, M.J.; Okada, K.; Oh-Hara, T.; Ogura, H.; Fujita, N.; Katayama, R. Mechanisms of Resistance to NTRK Inhibitors and Therapeutic Strategies in NTRK1-Rearranged Cancers. Mol. Cancer Ther., 2017, 16(10), 2130-2143.
[http://dx.doi.org/10.1158/1535-7163.MCT-16-0909] [PMID: 28751539]
[91]
Hilberg, F.; Roth, G.J.; Krssak, M.; Kautschitsch, S.; Sommergruber, W.; Tontsch-Grunt, U.; Garin-Chesa, P.; Bader, G.; Zoephel, A.; Quant, J.; Heckel, A.; Rettig, W.J. BIBF 1120: triple angiokinase inhibitor with sustained receptor blockade and good antitumor efficacy. Cancer Res., 2008, 68(12), 4774-4782.
[http://dx.doi.org/10.1158/0008-5472.CAN-07-6307] [PMID: 18559524]
[92]
O’Hare, T.; Shakespeare, W.C.; Zhu, X.; Eide, C.A.; Rivera, V.M.; Wang, F.; Adrian, L.T.; Zhou, T.; Huang, W.S.; Xu, Q.; Metcalf, C.A., III; Tyner, J.W.; Loriaux, M.M.; Corbin, A.S.; Wardwell, S.; Ning, Y.; Keats, J.A.; Wang, Y.; Sundaramoorthi, R.; Thomas, M.; Zhou, D.; Snodgrass, J.; Commodore, L.; Sawyer, T.K.; Dalgarno, D.C.; Deininger, M.W.; Druker, B.J.; Clackson, T. AP24534, a pan-BCR-ABL inhibitor for chronic myeloid leukemia, potently inhibits the T315I mutant and overcomes mutation-based resistance. Cancer Cell, 2009, 16(5), 401-412.
[http://dx.doi.org/10.1016/j.ccr.2009.09.028] [PMID: 19878872]
[93]
Cocco, E.; Scaltriti, M.; Drilon, A. NTRK fusion-positive cancers and TRK inhibitor therapy. Nat. Rev. Clin. Oncol., 2018, 15(12), 731-747.
[http://dx.doi.org/10.1038/s41571-018-0113-0] [PMID: 30333516]
[94]
Drilon, A.; Ou, S.I.; Cho, B.C.; Kim, D.W.; Lee, J.; Lin, J.J.; Zhu, V.W.; Ahn, M.J.; Camidge, D.R.; Nguyen, J.; Zhai, D.; Deng, W.; Huang, Z.; Rogers, E.; Liu, J.; Whitten, J.; Lim, J.K.; Stopatschinskaja, S.; Hyman, D.M.; Doebele, R.C.; Cui, J.J.; Shaw, A.T. Repotrectinib (TPX-0005) Is a Next-Generation ROS1/TRK/ALK Inhibitor That Potently Inhibits ROS1/TRK/ALK Solvent- Front Mutations. Cancer Discov., 2018, 8(10), 1227-1236.
[http://dx.doi.org/10.1158/2159-8290.CD-18-0484] [PMID: 30093503]
[95]
Drilon, A.; Nagasubramanian, R.; Blake, J.F.; Ku, N.; Tuch, B.B.; Ebata, K.; Smith, S.; Lauriault, V.; Kolakowski, G.R.; Brandhuber, B.J.; Larsen, P.D.; Bouhana, K.S.; Winski, S.L.; Hamor, R.; Wu, W.I.; Parker, A.; Morales, T.H.; Sullivan, F.X.; DeWolf, W.E.; Wollenberg, L.A.; Gordon, P.R.; Douglas-Lindsay, D.N.; Scaltriti, M.; Benayed, R.; Raj, S.; Hanusch, B.; Schram, A.M.; Jonsson, P.; Berger, M.F.; Hechtman, J.F.; Taylor, B.S.; Andrews, S.; Rothenberg, S.M.; Hyman, D.M. A Next-Generation TRK Kinase Inhibitor Overcomes Acquired Resistance to Prior TRK Kinase Inhibition in Patients with TRK Fusion-Positive Solid Tumors. Cancer Discov., 2017, 7(9), 963-972.
[http://dx.doi.org/10.1158/2159-8290.CD-17-0507] [PMID: 28578312]
[96]
O'Reilly, E. M.; Hechtman, J. F. Tumour response to TRK inhibition in a patient with pancreatic adenocarcinoma harbouring an NTRK gene fusion. Ann Oncol, 2019, 30(8), viii36-viii40.

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