publication . Other literature type . Article . 2018

Inhibiting TRK Proteins in Clinical Cancer Therapy

Hui-Wen Lo; Allison M. Lange;
Open Access
  • Published: 01 Apr 2018
  • Publisher: MDPI AG
Abstract
<jats:p>Gene rearrangements resulting in the aberrant activity of tyrosine kinases have been identified as drivers of oncogenesis in a variety of cancers. The tropomyosin receptor kinase (TRK) family of tyrosine receptor kinases is emerging as an important target for cancer therapeutics. The TRK family contains three members, TRKA, TRKB, and TRKC, and these proteins are encoded by the genes NTRK1, NTRK2, and NTRK3, respectively. To activate TRK receptors, neurotrophins bind to the extracellular region stimulating dimerization, phosphorylation, and activation of downstream signaling pathways. Major known downstream pathways include RAS/MAPK/ERK, PLCγ, and PI3K/Ak...
Read more
doi: 10.3390/cancers10040105
pmc: PMC5923360
pmid: 29617282
Subjects
Medical Subject Headings: nervous systemanimal structuresembryonic structuresenzymes and coenzymes (carbohydrates)
free text keywords: Review, NTRK gene fusions, TRKA, TRKB, TRKC, tyrosine kinase inhibitor, cancer, neurotrophin, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282, Cancer Research, Oncology, Tyrosine kinase, Kinase, Tropomyosin receptor kinase B, Tropomyosin receptor kinase C, MAPK/ERK pathway, Biology, Trk receptor, Tyrosine-kinase inhibitor, medicine.drug_class, medicine, Tropomyosin receptor kinase A
Related Organizations
Funded by
NIH| Truncated GLI1 In Glioblastoma
Project
Truncated GLI1 In Glioblastoma
  • Funder: National Institutes of Health (NIH)
  • Project Code: 3R01NS087169-03S1
  • Funding stream: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
Download fromView all 5 versions
Europe PubMed Central
Article . 2018
Provider: PubMed Central
Cancers
Article . 2018
Provider: DOAJ-Articles
Cancers
Article . 2018
Provider: Crossref
Cancers
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Provider: UnpayWall
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97 references, page 1 of 7

1. 2. 3. 4. 5. 6. 7. 8. 9. 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.; 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. 2017, 7, 400-409. [CrossRef] [PubMed]

Nakagawara, A. Trk receptor tyrosine kinases: A bridge between cancer and neural development. Cancer Lett. 2001, 169, 107-114. [CrossRef] [OpenAIRE]

Lagadec, C.; Meignan, S.; Adriaenssens, E.; Foveau, B.; Vanhecke, E.; Romon, R.; Toillon, R.A.; Oxombre, B.; Hondermarck, H.; Le Bourhis, X. TrkA overexpression enhances growth and metastasis of breast cancer cells. Oncogene 2009, 28, 1960-1970. [CrossRef] [PubMed] [OpenAIRE]

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. [CrossRef] [PubMed] Ardini, E.; Menichincheri, M.; Banfi, P.; Bosotti, R.; De Ponti, C.; Pulci, R.; Ballinari, D.; Ciomei, M.; Texido, G.; Degrassi, A.; et al. Entrectinib, a Pan-TRK, ROS1, and ALK Inhibitor with Activity in Multiple Molecularly Defined Cancer Indications. Mol. Cancer Ther. 2016, 15, 628-639. [CrossRef] [PubMed] Allen, S.J.; Wilcock, G.K.; Dawbarn, D. Profound and selective loss of catalytic TrkB immunoreactivity in Alzheimer's disease. Biochem. Biophys. Res. Commun. 1999, 264, 648-651. [CrossRef] [PubMed] Hashimoto, T.; Bergen, S.E.; Nguyen, Q.L.; Xu, B.; Monteggia, L.M.; Pierri, J.N.; Sun, Z.; Sampson, A.R.; Lewis, D.A. Relationship of brain-derived neurotrophic factor and its receptor TrkB to altered inhibitory prefrontal circuitry in schizophrenia. J. Neurosci. 2005, 25, 372-383. [CrossRef] [PubMed] Coppola, V.; Barrick, C.A.; Southon, E.A.; Celeste, A.; Wang, K.; Chen, B.; Haddad, E.-B.; Yin, J.; Nussenzweig, A.; Subramaniam, A.; et al. Ablation of TrkA function in the immune system causes B cell abnormalities. Development 2004, 131, 5185-5195. [CrossRef] [PubMed] Singer, H.S.; Hansen, B.; Martinie, D.; Karp, C.L. Mitogenesis in glioblastoma multiforme cell lines: A role for NGF and its TrkA receptors. J. Neurooncol. 1999, 45, 1-8. [CrossRef] [PubMed] [OpenAIRE]

10. Indo, Y.; Mardy, S.; Miura, Y.; Moosa, A.; Ismail, E.A.; Toscano, E.; Andria, G.; Pavone, V.; Brown, D.L.; Brooks, A.; et al. Congenital insensitivity to pain with anhidrosis (CIPA): Novel mutations of the TRKA (NTRK1) gene, a putative uniparental disomy, and a linkage of the mutant TRKA and PKLR genes in a family with CIPA and pyruvate kinase deficiency. Hum. Mutat. 2001, 18, 308-318. [CrossRef] [PubMed]

11. Morgensztern, D.; Campo, M.J.; Dahlberg, S.E.; Doebele, R.C.; Garon, E.; Gerber, D.E.; Goldberg, S.B.; Hammerman, P.S.; Heist, R.S.; Hensing, T.; et al. Molecularly targeted therapies in non-small-cell lung cancer annual update 2014. J. Thorac. Oncol. 2015, 10, S1-S63. [CrossRef] [PubMed] [OpenAIRE]

12. Indo, Y. Neurobiology of pain, interoception and emotional response: Lessons from nerve growth factor-dependent neurons. Eur. J. Neurosci. 2014, 39, 375-391. [CrossRef] [PubMed] [OpenAIRE]

13. Tejeda, G.S.; Diaz-Guerra, M. Integral Characterization of Defective BDNF/TrkB Signalling in Neurological and Psychiatric Disorders Leads the Way to New Therapies. Int. J. Mol. Sci. 2017, 18, 268. [CrossRef] [PubMed]

14. Su, A.I.; Wiltshire, T.; Batalov, S.; Lapp, H.; Ching, K.A.; Block, D.; Zhang, J.; Soden, R.; Hayakawa, M.; Kreiman, G.; et al. A gene atlas of the mouse and human protein-encoding transcriptomes. Proc. Natl. Acad. Sci. USA 2004, 101, 6062-6067. [CrossRef] [PubMed]

15. 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, 373-387. [CrossRef] [OpenAIRE]

16. Ferrer, I.; Marin, C.; Rey, M.J.; Ribalta, T.; Goutan, E.; Blanco, R.; Tolosa, E.; Marti, E. BDNF and full-length and truncated TrkB expression in Alzheimer disease. Implications in therapeutic strategies. J. Neuropathol. Exp. Neurol. 1999, 58, 729-739. [CrossRef] [PubMed]

17. Fenner, M.E.; Achim, C.L.; Fenner, B.M. Expression of full-length and truncated TrkB in human striatum and substantia nigra neurons: Implications for Parkinson's disease. J. Mol. Histol. 2014, 45, 349-361. [CrossRef] [PubMed]

18. Krishnan, V.; Nestler, E.J. Linking molecules to mood: New insight into the biology of depression. Am. J. Psychiatry 2010, 167, 1305-1320. [CrossRef] [PubMed]

19. Ernst, C.; Deleva, V.; Deng, X.; Sequeira, A.; Pomarenski, A.; Klempan, T.; Ernst, N.; Quirion, R.; Gratton, A.; Szyf, M.; et al. Alternative splicing, methylation state, and expression profile of tropomyosin-related kinase B in the frontal cortex of suicide completers. Arch. Gen. Psychiatry 2009, 66, 22-32. [CrossRef] [PubMed]

20. Dwivedi, Y.; Rizavi, H.S.; Conley, R.R.; Roberts, R.C.; Tamminga, C.A.; Pandey, G.N. Altered gene expression of brain-derived neurotrophic factor and receptor tyrosine kinase B in postmortem brain of suicide subjects. Arch. Gen. Psychiatry 2003, 60, 804-815. [CrossRef] [PubMed]

97 references, page 1 of 7
Related research
Abstract
<jats:p>Gene rearrangements resulting in the aberrant activity of tyrosine kinases have been identified as drivers of oncogenesis in a variety of cancers. The tropomyosin receptor kinase (TRK) family of tyrosine receptor kinases is emerging as an important target for cancer therapeutics. The TRK family contains three members, TRKA, TRKB, and TRKC, and these proteins are encoded by the genes NTRK1, NTRK2, and NTRK3, respectively. To activate TRK receptors, neurotrophins bind to the extracellular region stimulating dimerization, phosphorylation, and activation of downstream signaling pathways. Major known downstream pathways include RAS/MAPK/ERK, PLCγ, and PI3K/Ak...
Read more
doi: 10.3390/cancers10040105
pmc: PMC5923360
pmid: 29617282
Subjects
Medical Subject Headings: nervous systemanimal structuresembryonic structuresenzymes and coenzymes (carbohydrates)
free text keywords: Review, NTRK gene fusions, TRKA, TRKB, TRKC, tyrosine kinase inhibitor, cancer, neurotrophin, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282, Cancer Research, Oncology, Tyrosine kinase, Kinase, Tropomyosin receptor kinase B, Tropomyosin receptor kinase C, MAPK/ERK pathway, Biology, Trk receptor, Tyrosine-kinase inhibitor, medicine.drug_class, medicine, Tropomyosin receptor kinase A
Related Organizations
Funded by
NIH| Truncated GLI1 In Glioblastoma
Project
Truncated GLI1 In Glioblastoma
  • Funder: National Institutes of Health (NIH)
  • Project Code: 3R01NS087169-03S1
  • Funding stream: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
Download fromView all 5 versions
Europe PubMed Central
Article . 2018
Provider: PubMed Central
Cancers
Article . 2018
Provider: DOAJ-Articles
Cancers
Article . 2018
Provider: Crossref
Cancers
Article
Provider: UnpayWall
View more
97 references, page 1 of 7

1. 2. 3. 4. 5. 6. 7. 8. 9. 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.; 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. 2017, 7, 400-409. [CrossRef] [PubMed]

Nakagawara, A. Trk receptor tyrosine kinases: A bridge between cancer and neural development. Cancer Lett. 2001, 169, 107-114. [CrossRef] [OpenAIRE]

Lagadec, C.; Meignan, S.; Adriaenssens, E.; Foveau, B.; Vanhecke, E.; Romon, R.; Toillon, R.A.; Oxombre, B.; Hondermarck, H.; Le Bourhis, X. TrkA overexpression enhances growth and metastasis of breast cancer cells. Oncogene 2009, 28, 1960-1970. [CrossRef] [PubMed] [OpenAIRE]

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. [CrossRef] [PubMed] Ardini, E.; Menichincheri, M.; Banfi, P.; Bosotti, R.; De Ponti, C.; Pulci, R.; Ballinari, D.; Ciomei, M.; Texido, G.; Degrassi, A.; et al. Entrectinib, a Pan-TRK, ROS1, and ALK Inhibitor with Activity in Multiple Molecularly Defined Cancer Indications. Mol. Cancer Ther. 2016, 15, 628-639. [CrossRef] [PubMed] Allen, S.J.; Wilcock, G.K.; Dawbarn, D. Profound and selective loss of catalytic TrkB immunoreactivity in Alzheimer's disease. Biochem. Biophys. Res. Commun. 1999, 264, 648-651. [CrossRef] [PubMed] Hashimoto, T.; Bergen, S.E.; Nguyen, Q.L.; Xu, B.; Monteggia, L.M.; Pierri, J.N.; Sun, Z.; Sampson, A.R.; Lewis, D.A. Relationship of brain-derived neurotrophic factor and its receptor TrkB to altered inhibitory prefrontal circuitry in schizophrenia. J. Neurosci. 2005, 25, 372-383. [CrossRef] [PubMed] Coppola, V.; Barrick, C.A.; Southon, E.A.; Celeste, A.; Wang, K.; Chen, B.; Haddad, E.-B.; Yin, J.; Nussenzweig, A.; Subramaniam, A.; et al. Ablation of TrkA function in the immune system causes B cell abnormalities. Development 2004, 131, 5185-5195. [CrossRef] [PubMed] Singer, H.S.; Hansen, B.; Martinie, D.; Karp, C.L. Mitogenesis in glioblastoma multiforme cell lines: A role for NGF and its TrkA receptors. J. Neurooncol. 1999, 45, 1-8. [CrossRef] [PubMed] [OpenAIRE]

10. Indo, Y.; Mardy, S.; Miura, Y.; Moosa, A.; Ismail, E.A.; Toscano, E.; Andria, G.; Pavone, V.; Brown, D.L.; Brooks, A.; et al. Congenital insensitivity to pain with anhidrosis (CIPA): Novel mutations of the TRKA (NTRK1) gene, a putative uniparental disomy, and a linkage of the mutant TRKA and PKLR genes in a family with CIPA and pyruvate kinase deficiency. Hum. Mutat. 2001, 18, 308-318. [CrossRef] [PubMed]

11. Morgensztern, D.; Campo, M.J.; Dahlberg, S.E.; Doebele, R.C.; Garon, E.; Gerber, D.E.; Goldberg, S.B.; Hammerman, P.S.; Heist, R.S.; Hensing, T.; et al. Molecularly targeted therapies in non-small-cell lung cancer annual update 2014. J. Thorac. Oncol. 2015, 10, S1-S63. [CrossRef] [PubMed] [OpenAIRE]

12. Indo, Y. Neurobiology of pain, interoception and emotional response: Lessons from nerve growth factor-dependent neurons. Eur. J. Neurosci. 2014, 39, 375-391. [CrossRef] [PubMed] [OpenAIRE]

13. Tejeda, G.S.; Diaz-Guerra, M. Integral Characterization of Defective BDNF/TrkB Signalling in Neurological and Psychiatric Disorders Leads the Way to New Therapies. Int. J. Mol. Sci. 2017, 18, 268. [CrossRef] [PubMed]

14. Su, A.I.; Wiltshire, T.; Batalov, S.; Lapp, H.; Ching, K.A.; Block, D.; Zhang, J.; Soden, R.; Hayakawa, M.; Kreiman, G.; et al. A gene atlas of the mouse and human protein-encoding transcriptomes. Proc. Natl. Acad. Sci. USA 2004, 101, 6062-6067. [CrossRef] [PubMed]

15. 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, 373-387. [CrossRef] [OpenAIRE]

16. Ferrer, I.; Marin, C.; Rey, M.J.; Ribalta, T.; Goutan, E.; Blanco, R.; Tolosa, E.; Marti, E. BDNF and full-length and truncated TrkB expression in Alzheimer disease. Implications in therapeutic strategies. J. Neuropathol. Exp. Neurol. 1999, 58, 729-739. [CrossRef] [PubMed]

17. Fenner, M.E.; Achim, C.L.; Fenner, B.M. Expression of full-length and truncated TrkB in human striatum and substantia nigra neurons: Implications for Parkinson's disease. J. Mol. Histol. 2014, 45, 349-361. [CrossRef] [PubMed]

18. Krishnan, V.; Nestler, E.J. Linking molecules to mood: New insight into the biology of depression. Am. J. Psychiatry 2010, 167, 1305-1320. [CrossRef] [PubMed]

19. Ernst, C.; Deleva, V.; Deng, X.; Sequeira, A.; Pomarenski, A.; Klempan, T.; Ernst, N.; Quirion, R.; Gratton, A.; Szyf, M.; et al. Alternative splicing, methylation state, and expression profile of tropomyosin-related kinase B in the frontal cortex of suicide completers. Arch. Gen. Psychiatry 2009, 66, 22-32. [CrossRef] [PubMed]

20. Dwivedi, Y.; Rizavi, H.S.; Conley, R.R.; Roberts, R.C.; Tamminga, C.A.; Pandey, G.N. Altered gene expression of brain-derived neurotrophic factor and receptor tyrosine kinase B in postmortem brain of suicide subjects. Arch. Gen. Psychiatry 2003, 60, 804-815. [CrossRef] [PubMed]

97 references, page 1 of 7
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