Skip to main content
SpringerLink
Log in

NTRK-Targeted Therapy in Lung Cancer

  • Chapter
  • First Online:
Targeted Therapies for Lung Cancer

Part of the book series: Current Cancer Research ((CUCR))

  • 827 Accesses

Abstract

Gene rearrangements or fusions as a tumorigenic genomic driver event have been identified as a common recurrent occurrence in a variety of human malignancies. The neurotrophic tyrosine receptor kinase gene family contains NTRK1, NTRK2, and NTRK3, which encode the proteins tropomyosin receptor kinase A, B, and C (TRKA, TRKB, TRKC), respectively. TRKA, TRKB, and TRKC can be activated by the specific ligands, such as nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin-3 (NT3). Interestingly, although NTRK gene fusions occur relatively rarely in human cancers overall, they have been found to be present broadly in many different tumor types, including both pediatric and adult malignancies. The recognition of NTRK fusions as driver genomic event in recent years have prompted impactful clinical therapeutic development which demonstrated the efficacy and safety of TRK inhibitors, with a recent approval of larotrectinib by the US Food and Drug Administration in a cancer-agnostic manner for NTRK fusion-positive cancers. Here, we reviewed the biology of NTRK gene fusions, antitumor activity of TRK inhibitors, clinical trials development, and challenges and future perspectives of NTRK-targeted therapies in human cancer with a special focus on lung cancer.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 109.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 139.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 139.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Allen SJ, Wilcock GK, Dawbarn D. Profound and selective loss of catalytic TrkB immunoreactivity in Alzheimer’s disease. Biochem Biophys Res Commun. 1999;264:648–51. https://doi.org/10.1006/bbrc.1999.1561.

    Article  CAS  PubMed  Google Scholar 

  2. Amatu A, Sartore-Bianchi A, Siena S. NTRK gene fusions as novel targets of cancer therapy across multiple tumour types. ESMO Open. 2016;1:e000023. https://doi.org/10.1136/esmoopen-2015-000023.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Ardini E, Menichincheri M, Banfi P, et al. Entrectinib, a pan-TRK, ROS1, and ALK inhibitor with activity in multiple molecularly defined cancer indications. Mol Cancer Ther. 2016;15:628–39. https://doi.org/10.1158/1535-7163.MCT-15-0758.

    Article  CAS  PubMed  Google Scholar 

  4. Arkenau HT, Sachdev JC, Mita MM, et al. Phase (Ph) 1/2a study of TSR-011, a potent inhibitor of ALK and TRK, in advanced solid tumors including crizotinib-resistant ALK positive non-small cell lung cancer. J Clin Oncol. 2015;33:8063–8063. https://doi.org/10.1200/jco.2015.33.15_suppl.8063.

    Article  Google Scholar 

  5. Bollig-Fischer A, Michelhaugh SK, Wijesinghe P, et al. Cytogenomic profiling of breast cancer brain metastases reveals potential for repurposing targeted therapeutics. Oncotarget. 2015;6:14614–24. https://doi.org/10.18632/oncotarget.3786.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Boon E, Valstar MH, van der Graaf WTA, Bloemena E, Willems SM, Meeuwis CA, Slootweg PJ, Smit LA, Merkx MAW, Takes RP, Kaanders JHAM, Groenen PJTA, Flucke UE, van Herpen CML. Clinicopathological characteristics and outcome of 31 patients with ETV6-NTRK3 fusion geneconfirmed (mammary analogue) secretory carcinoma of salivary glands. Oral Oncol. 2018;82:29–33.

    Article  CAS  PubMed  Google Scholar 

  7. Brenca M, Rossi S, Polano M, Gasparotto D, Zanatta L, Racanelli D, Valori L, Lamon S, Dei Tos AP, Maestro R. Transcriptome sequencing identifies ETV6-NTRK3 as a gene fusion involved in GIST. J Pathol. 2016;238(4):543–9.

    Article  CAS  PubMed  Google Scholar 

  8. Brodeur GM, Minturn JE, Ho R, et al. Trk receptor expression and inhibition in neuroblastomas. Clin Cancer Res. 2009;15:3244–50. https://doi.org/10.1158/1078-0432.CCR-08-1815.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Créancier L, Vandenberghe I, Gomes B, Dejean C, Blanchet JC, Meilleroux J, Guimbaud R, Selves J, Kruczynski A. Chromosomal rearrangements involving the NTRK1 gene in colorectal carcinoma. Cancer Lett. 2015;365(1):107–11.

    Article  PubMed  Google Scholar 

  10. Davis JL, Lockwood CM, Albert CM, Tsuchiya K, Hawkins DS, Rudzinski ER. Infantile NTRK-associated Mesenchymal Tumors. Pediatr Dev Pathol. 2018;21(1):68–78.

    Article  PubMed  Google Scholar 

  11. De Farias CB, Heinen TE, Dos Santos RP, et al. BDNF/TrkB signaling protects HT-29 human colon cancer cells from EGFR inhibition. Biochem Biophys Res Commun. 2012;425:328–32. https://doi.org/10.1016/j.bbrc.2012.07.091.

    Article  CAS  PubMed  Google Scholar 

  12. Doebele RC, Davis LE, Vaishnavi A, et al. An oncogenic NTRK fusion in a patient with soft-tissue sarcoma with response to the tropomyosin-related kinase inhibitor LOXO-101. Cancer Discov. 2015;5:1049–57. https://doi.org/10.1158/2159-8290.CD-15-0443.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Douma S, Van Laar T, Zevenhoven J, et al. Suppression of anoikis and induction of metastasis by the neurotrophic receptor TrkB. Nature. 2004;430:1034–9. https://doi.org/10.1038/nature02765.

    Article  CAS  PubMed  Google Scholar 

  14. Drilon A, Laetsch TW, Kummar S, et al. Efficacy of larotrectinib in TRK fusion-positive cancers in adults and children. N Engl J Med. 2018a;378:731–9. https://doi.org/10.1056/NEJMoa1714448.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Drilon A, Li G, Dogan S, et al. 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;27:920–6. https://doi.org/10.1093/annonc/mdw042.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Drilon A, Nagasubramanian R, Blake JF, et al. A next-generation TRK kinase inhibitor overcomes acquired resistance to prior TRK kinase inhibition in patients with TRK fusion-positive solid tumors. Cancer Discov. 2017a;7:963–72. https://doi.org/10.1158/2159-8290.CD-17-0507.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Drilon A, Ou SH, Cho BC, et al. Repotrectinib (TPX-0005) is a next-generation ROS1/TRK/ALK inhibitor that potently inhibits ROS1/TRK/ALK solvent- front mutations. Cancer Discov. 2018b;8:1227–36. https://doi.org/10.1158/2159-8290.CD-18-0484.

    Article  CAS  PubMed  Google Scholar 

  18. Drilon A, Siena S, Ou SH, et al. 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. 2017b;7:400–9. https://doi.org/10.1158/2159-8290.CD-16-1237.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. DuBois SG, Laetsch TW, Federman N, et al. The use of neoadjuvant larotrectinib in the management of children with locally advanced TRK fusion sarcomas. Cancer. 2018;124:4241–7. https://doi.org/10.1002/cncr.31701.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Eggert A, Grotzer MA, Ikegaki N, et al. Expression of the neurotrophin receptor TrkB is associated with unfavorable outcome in Wilms’ tumor. J Clin Oncol. 2001;19:689–96. https://doi.org/10.1200/JCO.2001.19.3.689.

    Article  CAS  PubMed  Google Scholar 

  21. Eguchi M, Eguchi-Ishimae M, Tojo A, Morishita K, Suzuki K, Sato Y, Kudoh S, Tanaka K, Setoyama M, Nagamura F, Asano S, Kamada N. Fusion of ETV6 to neurotrophin-3 receptor TRKC in acute myeloid leukemia with t(12;15)(p13;q25). Blood. 1999;93(4):1355–63.

    CAS  PubMed  Google Scholar 

  22. Farago AF, Le LP, Zheng Z, et al. Durable clinical response to entrectinib in NTRK1-rearranged non-small cell lung cancer. J Thorac Oncol. 2015;10:1670–4. https://doi.org/10.1097/01.JTO.0000473485.38553.f0.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Farago AF, Taylor MS, Doebele RC et al Clinicopathologic features of non-small-cell lung cancer harboring an NTRK gene fusion. JCO Precis Oncol. 2018;2018. https://doi.org/10.1200/PO.18.00037.

  24. Ferrer I, Marín C, Rey MJ, et al. BDNF and full-length and truncated TrkB expression in Alzheimer disease. Implications in therapeutic strategies. J Neuropathol Exp Neurol. 1999;58:729–39.

    Article  CAS  PubMed  Google Scholar 

  25. Gao J, Aksoy BA, Dogrusoz U, et al. Integrative analysis of complex cancer genomics and clinical profiles using the cBioPortal. Sci Signal. 2013;6:pl1. https://doi.org/10.1126/scisignal.2004088.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Gatalica Z, Xiu J, Swensen J, et al. Molecular characterization of cancers with NTRK gene fusions. Mod Pathol. 2019;32:147–53. https://doi.org/10.1038/s41379-018-0118-3.

    Article  CAS  PubMed  Google Scholar 

  27. Greco A, Miranda C, Pierotti MA. Rearrangements of NTRK1 gene in papillary thyroid carcinoma. Mol Cell Endocrinol. 2010;321:44–9. https://doi.org/10.1016/j.mce.2009.10.009.

    Article  CAS  PubMed  Google Scholar 

  28. Gromnitza S, Lepa C, Weide T, et al. Tropomyosin-related kinase C (TrkC) enhances podocyte migration by ERK-mediated WAVE2 activation. FASEB J. 2018;32:1665–76. https://doi.org/10.1096/fj.201700703R.

    Article  CAS  PubMed  Google Scholar 

  29. Indo Y. Neurobiology of pain, interoception and emotional response: lessons from nerve growth factor-dependent neurons. Eur J Neurosci. 2014;39:375–91. https://doi.org/10.1111/ejn.12448.

    Article  PubMed  Google Scholar 

  30. Ivanov SV, Panaccione A, Brown B, et al. TrkC signaling is activated in adenoid cystic carcinoma and requires NT-3 to stimulate invasive behavior. Oncogene. 2013;32:3698–710. https://doi.org/10.1038/onc.2012.377.

    Article  CAS  PubMed  Google Scholar 

  31. Kaplan DR, Martin-Zanca D, Parada LF. Tyrosine phosphorylation and tyrosine kinase activity of the trk proto-oncogene product induced by NGF. Nature. 1991;350:158–60. https://doi.org/10.1038/350158a0.

    Article  CAS  PubMed  Google Scholar 

  32. Kaplan DR, Miller FD. Neurotrophin signal transduction in the nervous system. Curr Opin Neurobiol. 2000;10:381–91.

    Article  CAS  PubMed  Google Scholar 

  33. Kheder ES, Hong DS. Emerging targeted therapy for tumors with NTRK fusion proteins. Clin Cancer Res. 2018;24:5807–14. https://doi.org/10.1158/1078-0432.CCR-18-1156.

    Article  PubMed  Google Scholar 

  34. Kim J, Lee Y, Cho HJ, Lee YE, An J, Cho GH, Ko YH, Joo KM, Nam DH. NTRK1 fusion in glioblastoma multiforme. PLoS One. 2014;9(3):e91940.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Kim MS, Jeong J, Seo J, et al. Dysregulated JAK2 expression by TrkC promotes metastasis potential, and EMT program of metastatic breast cancer. Sci Rep. 2016;6:33899. https://doi.org/10.1038/srep33899.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Kimura S, Harada T, Ijichi K, et al. 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. https://doi.org/10.1016/j.lungcan.2018.04.005.

    Article  PubMed  Google Scholar 

  37. Klein R, Nanduri V, Jing S, et al. The trkB tyrosine protein kinase is a receptor for brain-derived neurotrophic factor and neurotrophin-3. Cell. 1991;66:395–403.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Knezevich SR, McFadden DE, Tao W, et al. A novel ETV6-NTRK3 gene fusion in congenital fibrosarcoma. Nat Genet. 1998;18:184–7. https://doi.org/10.1038/ng0298-184.

    Article  CAS  PubMed  Google Scholar 

  39. Konicek BW, Capen AR, Credille KM, et al. Merestinib (LY2801653) inhibits neurotrophic receptor kinase (NTRK) and suppresses growth of NTRK fusion bearing tumors. Oncotarget. 2018;9:13796–806. https://doi.org/10.18632/oncotarget.24488.

    Article  PubMed  PubMed Central  Google Scholar 

  40. Laetsch TW, DuBois SG, Mascarenhas L, et al. Larotrectinib for paediatric solid tumours harbouring NTRK gene fusions: phase 1 results from a multicentre, open-label, phase 1/2 study. Lancet Oncol. 2018;19:705–14. https://doi.org/10.1016/S1470-2045(18)30119-0.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Lamballe F, Klein R, Barbacid M. trkC, a new member of the trk family of tyrosine protein kinases, is a receptor for neurotrophin-3. Cell. 1991;66:967–79.

    Article  CAS  PubMed  Google Scholar 

  42. Lange AM, Lo HW. Inhibiting TRK proteins in clinical cancer therapy. Cancers (Basel). 2018;10. https://doi.org/10.3390/cancers10040105.

    Article  PubMed Central  Google Scholar 

  43. Makretsov N, He M, Hayes M, et al. A fluorescence in situ hybridization study of ETV6-NTRK3 fusion gene in secretory breast carcinoma. Genes Chromosomes Cancer. 2004;40:152–7. https://doi.org/10.1002/gcc.20028.

    Article  CAS  PubMed  Google Scholar 

  44. Mardy S, Miura Y, Endo F, et al. Congenital insensitivity to pain with anhidrosis: novel mutations in the TRKA (NTRK1) gene encoding a high-affinity receptor for nerve growth factor. Am J Hum Genet. 1999;64:1570–9. https://doi.org/10.1086/302422.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Martin-Zanca D, Hughes SH, Barbacid M. A human oncogene formed by the fusion of truncated tropomyosin and protein tyrosine kinase sequences. Nature. 1986;319:743–8. https://doi.org/10.1038/319743a0.

    Article  CAS  PubMed  Google Scholar 

  46. Milione M, Ardini E, Christiansen J, Valtorta E, Veronese S, Bosotti R, Pellegrinelli A, Testi A, Pietrantonio F, Fucà G, Wei G, Murphy D, Siena S, Isacchi A, De Braud F. Identification and characterization of a novel SCYL3-NTRK1 rearrangement in a colorectal cancer patient. Oncotarget. 2017;8(33):55353–60.

    Article  PubMed  PubMed Central  Google Scholar 

  47. Mok TS, Wu YL, Thongprasert S, et al. Gefitinib or carboplatin–paclitaxel in pulmonary adenocarcinoma. N Engl J Med. 2009;361:947–57.

    Article  CAS  PubMed  Google Scholar 

  48. Nakagawara A. Trk receptor tyrosine kinases: a bridge between cancer and neural development. Cancer Lett. 2001;169:107–14.

    Article  CAS  PubMed  Google Scholar 

  49. Nakagawara A, Liu XG, Ikegaki N, et al. Cloning and chromosomal localization of the human TRK-B tyrosine kinase receptor gene (NTRK2). Genomics. 1995;25:538–46.

    Article  CAS  PubMed  Google Scholar 

  50. Ni J, Xie S, Ramkissoon SH, Luu V, Sun Y, Bandopadhayay P, Beroukhim R, Roberts TM, Stiles CD, Segal RA, Ligon KL, Hahn WC, Zhao JJ. Tyrosine receptor kinase B is a drug target in astrocytomas. Neuro Oncol. 2017;19(1):22–30.

    Article  CAS  PubMed  Google Scholar 

  51. Okamura K, Harada T, Wang S, et al. Expression of TrkB and BDNF is associated with poor prognosis in non-small cell lung cancer. Lung Cancer. 2012;78:100–6. https://doi.org/10.1016/j.lungcan.2012.07.011.

    Article  PubMed  Google Scholar 

  52. Pulciani S, Santos E, Lauver AV, et al. Oncogenes in solid human tumours. Nature. 1982;300:539–42.

    Article  CAS  PubMed  Google Scholar 

  53. Ross JS, Wang K, Gay L, Al-Rohil R, Rand JV, Jones DM, Lee HJ, Sheehan CE, Otto GA, Palmer G, Yelensky R, Lipson D, Morosini D, Hawryluk M, Catenacci DV, Miller VA, Churi C, Ali S, Stephens PJ. New routes to targeted therapy of intrahepatic cholangiocarcinomas revealed by next-generationsequencing. Oncologist. 2014;19(3):235–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Rubin JB, Segal RA. Growth, survival and migration: the Trk to cancer. Cancer Treat Res. 2003;115:1–18.

    CAS  PubMed  Google Scholar 

  55. Rubin BP, Chen CJ, Morgan TW, Xiao S, Grier HE, Kozakewich HP, Perez-Atayde AR, Fletcher JA. Congenital mesoblastic nephroma t(12;15) is associated with ETV6-NTRK3 gene fusion: cytogenetic and molecular relationship to congenital (infantile) fibrosarcoma. Am J Pathol. 1998;153(5):1451–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Rudzinski ER, Lockwood CM, Stohr BA, et al. Pan-Trk immunohistochemistry identifies NTRK rearrangements in pediatric mesenchymal tumors. Am J Surg Pathol. 2018;42:927–35. https://doi.org/10.1097/PAS.0000000000001062.

    Article  PubMed  Google Scholar 

  57. Russo M, Misale S, Wei G, et al. Acquired resistance to the TRK inhibitor entrectinib in colorectal cancer. Cancer Discov. 2016;6:36–44. https://doi.org/10.1158/2159-8290.CD-15-0940.

    Article  CAS  PubMed  Google Scholar 

  58. Salehi A, Verhaagen J, Dijkhuizen PA, et al. Co-localization of high-affinity neurotrophin receptors in nucleus basalis of Meynert neurons and their differential reduction in Alzheimer's disease. Neuroscience. 1996;75:373–87.

    Article  CAS  PubMed  Google Scholar 

  59. Sartore-Bianchi A, Ardini E, Bosotti R et al. Sensitivity to entrectinib associated with a novel LMNA-NTRK1 gene fusion in metastatic colorectal cancer. J Natl Cancer Inst. 2016;108. https://doi.org/10.1093/jnci/djv306.

  60. Shaw AT, Hsu PP, Awad MM, et al. Tyrosine kinase gene rearrangements in epithelial malignancies. Nat Rev Cancer. 2013;13:772–87. https://doi.org/10.1038/nrc3612.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Sigal D, Tartar M, Xavier M, et al. Activity of entrectinib in a patient with the first reported NTRK fusion in neuroendocrine cancer. J Natl Compr Cancer Netw. 2017;15:1317–22. https://doi.org/10.6004/jnccn.2017.7029.

    Article  Google Scholar 

  62. Singer HS, Hansen B, Martinie D, et al. Mitogenesis in glioblastoma multiforme cell lines: a role for NGF and its TrkA receptors. J Neuro-Oncol. 1999;45:1–8.

    Article  CAS  Google Scholar 

  63. Smith KM, Fagan PC, Pomari E, Germano G, Frasson C, Walsh C, Silverman I, Bonvini P, Li G. Antitumor activity of entrectinib, a Pan-TRK, ROS1, and ALK inhibitor, in ETV6-NTRK3-Positive acute myeloid leukemia. Mol Cancer Ther. 2018;17(2):455–63.

    CAS  PubMed  Google Scholar 

  64. Squinto SP, Stitt TN, Aldrich TH, et al. trkB encodes a functional receptor for brain-derived neurotrophic factor and neurotrophin-3 but not nerve growth factor. Cell. 1991;65:885–93.

    Article  CAS  PubMed  Google Scholar 

  65. Stransky N, Cerami E, Schalm S, Kim JL, Lengauer C. The landscape of kinase fusions in cancer. Nat Commun. 2014;5:4846.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Taylor J, Pavlick D, Yoshimi A, et al. Oncogenic TRK fusions are amenable to inhibition in hematologic malignancies. J Clin Invest. 2018;128:3819–25. https://doi.org/10.1172/JCI120787.

    Article  PubMed  PubMed Central  Google Scholar 

  67. Thiele CJ, Li Z, McKee AE. On Trk--the TrkB signal transduction pathway is an increasingly important target in cancer biology. Clin Cancer Res. 2009;15:5962–7. https://doi.org/10.1158/1078-0432.CCR-08-0651.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Tognon C, Garnett M, etal KE. The chimeric protein tyrosine kinase ETV6-NTRK3 requires both Ras-Erk1/2 and PI3-kinase-Akt signaling for fibroblast transformation. Cancer Res. 2001;61:8909–16.

    CAS  PubMed  Google Scholar 

  69. Vaishnavi A, Capelletti M, Le AT, et al. Oncogenic and drug-sensitive NTRK1 rearrangements in lung cancer. Nat Med. 2013;19:1469–72. https://doi.org/10.1038/nm.3352.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Valent A, Danglot G, Bernheim A. Mapping of the tyrosine kinase receptors trkA (NTRK1), trkB (NTRK2) and trkC(NTRK3) to human chromosomes 1q22, 9q22 and 15q25 by fluorescence in situ hybridization. Eur J Hum Genet. 1997;5:102–4.

    CAS  PubMed  Google Scholar 

  71. Weier HU, Rhein AP, Shadravan F, et al. Rapid physical mapping of the human trk protooncogene (NTRK1) to human chromosome 1q21-q22 by P1 clone selection, fluorescence in situ hybridization (FISH), and computer-assisted microscopy. Genomics. 1995;26:390–3.

    Article  CAS  PubMed  Google Scholar 

  72. Wiesner T, He J, Yelensky R, Esteve-Puig R, Botton T, Yeh I, Lipson D, Otto G, Brennan K, Murali R, Garrido M, Miller VA, Ross JS, Berger MF, Sparatta A, Palmedo G, Cerroni L, Busam KJ, Kutzner H, Cronin MT, Stephens PJ, Bastian BC. Kinase fusions are frequent in Spitz tumours and spitzoid melanomas. Nat Commun. 2014;5:3116.

    Article  PubMed  PubMed Central  Google Scholar 

  73. Wong V, Pavlick D, Brennan T, Yelensky R, Crawford J, Ross JS, Miller VA, Malicki D, Stephens PJ, Ali SM, Ahn H. Evaluation of a congenital infantile fibrosarcoma by comprehensive genomic profiling revealsan LMNA-NTRK1 gene fusion responsive to crizotinib. J Natl Cancer Inst. 2015;108:1. pii: djv307.

    Google Scholar 

  74. Wu G, Diaz AK, Paugh BS, Rankin SL, 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 HL, Boggs K, Vadodaria B, Yergeau D, Russell JC, Ochoa K, Fulton RS, Fulton LL, Jones C, Boop FA, Broniscer A, Wetmore C, Gajjar A, Ding L, Mardis ER, Wilson RK, Taylor MR, Downing JR, Ellison DW, Zhang J, Baker SJ. The genomic landscape of diffuse intrinsic pontine glioma and pediatric non-brainstem high-grade glioma. Nat Genet. 2014;46(5):444–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Yan SB, Um SL, Peek VL, et al. MET-targeting antibody (emibetuzumab) and kinase inhibitor (merestinib) as single agent or in combination in a cancer model bearing MET exon 14 skipping. Investig New Drugs. 2018;36:536–44. https://doi.org/10.1007/s10637-017-0545-x.

    Article  CAS  Google Scholar 

  76. Yeo GS, Hung CC, Rochford J, et al. A de novo mutation affecting human TrkB associated with severe obesity and developmental delay. Nat Neurosci. 2004;7:1187–9. https://doi.org/10.1038/nn1336.

    Article  CAS  PubMed  Google Scholar 

  77. Zheng Z, Liebers M, Zhelyazkova B, Cao Y, Panditi D, Lynch KD, Chen J, Robinson HE, Shim HS, Chmielecki J, Pao W, Engelman JA, Iafrate AJ, Le LP. Anchored multiplex PCR for targeted next-generation sequencing. Nat Med. 2014;20(12):1479–84.

    Article  CAS  PubMed  Google Scholar 

Download references

Conflicts of Interest

Advisory Board/Committee: AstraZeneca, Cymeta, Takeda, Caris Life Sciences

Speakers Bureau: Merck, Takeda, AstraZeneca, Bristol Myers-Squibb, Bayer

Research Funding (to Institution): AstraZeneca, Bristol Myers-Squibb, AbbVie, Loxo, CBT Pharmaceuticals, Pfizer, Cymeta Biopharmaceuticals, Incyte, Medimmune, Tesaro, XCovery, Spectrum, EpicentRx

Author information

Authors and Affiliations

  1. WVU Cancer Institute, Mary Babb Randolph Cancer Center, WVU Medicine, West Virginia University, Morgantown, WV, USA

    Xiaoliang Wu, Lin Zhu & Patrick C. Ma

Authors
  1. Xiaoliang Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Lin Zhu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Patrick C. Ma
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Patrick C. Ma .

Editor information

Editors and Affiliations

  1. Department of Medical Oncology and Therapeutics Research, City of Hope National Medical Center, Duarte, CA, USA

    Ravi Salgia

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Wu, X., Zhu, L., Ma, P.C. (2019). NTRK-Targeted Therapy in Lung Cancer. In: Salgia, R. (eds) Targeted Therapies for Lung Cancer. Current Cancer Research. Springer, Cham. https://doi.org/10.1007/978-3-030-17832-1_7

Download citation

  • DOI: https://doi.org/10.1007/978-3-030-17832-1_7

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-17831-4

  • Online ISBN: 978-3-030-17832-1

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation