Difference between revisions of "TRK fusions"
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*Merestinib. | *Merestinib. | ||
*Larotrectinib.<ref name=pmid29466156>{{Cite journal | last1 = Drilon | first1 = A. | last2 = Laetsch | first2 = TW. | last3 = Kummar | first3 = S. | last4 = DuBois | first4 = SG. | last5 = Lassen | first5 = UN. | last6 = Demetri | first6 = GD. | last7 = Nathenson | first7 = M. | last8 = Doebele | first8 = RC. | last9 = Farago | first9 = AF. | title = Efficacy of Larotrectinib in TRK Fusion-Positive Cancers in Adults and Children. | journal = N Engl J Med | volume = 378 | issue = 8 | pages = 731-739 | month = 02 | year = 2018 | doi = 10.1056/NEJMoa1714448 | PMID = 29466156 }}</ref> | *Larotrectinib.<ref name=pmid29466156>{{Cite journal | last1 = Drilon | first1 = A. | last2 = Laetsch | first2 = TW. | last3 = Kummar | first3 = S. | last4 = DuBois | first4 = SG. | last5 = Lassen | first5 = UN. | last6 = Demetri | first6 = GD. | last7 = Nathenson | first7 = M. | last8 = Doebele | first8 = RC. | last9 = Farago | first9 = AF. | title = Efficacy of Larotrectinib in TRK Fusion-Positive Cancers in Adults and Children. | journal = N Engl J Med | volume = 378 | issue = 8 | pages = 731-739 | month = 02 | year = 2018 | doi = 10.1056/NEJMoa1714448 | PMID = 29466156 }}</ref> | ||
*Entrectinib.<ref name=pmid26565381>{{Cite journal | last1 = Farago | first1 = AF. | last2 = Le | first2 = LP. | last3 = Zheng | first3 = Z. | last4 = Muzikansky | first4 = A. | last5 = Drilon | first5 = A. | last6 = Patel | first6 = M. | last7 = Bauer | first7 = TM. | last8 = Liu | first8 = SV. | last9 = Ou | first9 = SH. | title = Durable Clinical Response to Entrectinib in NTRK1-Rearranged Non-Small Cell Lung Cancer. | journal = J Thorac Oncol | volume = 10 | issue = 12 | pages = 1670-4 | month = Dec | year = 2015 | doi = 10.1097/01.JTO.0000473485.38553.f0 | PMID = 26565381 }}</ref> | |||
*Others. | *Others. | ||
Revision as of 10:29, 19 March 2019
TRK fusions are seen in many solid tumours of children and adults and have targeted drugs.[1]
General
Genes:[2]
- NTRK1.
- NTRK2.
- NTRK3.
Notes:
- The TRK genes are tropomyosine kinase receptors.
- Multiple fusion partners for each gene.
Testing:
- RNA-based next generation sequencing.
- Immunohistochemistry[3] - limited sensitivity?
Associations
Classic
- Mammary analogue secretory carcinoma (MASC) - ETV6-NTRK3.[4]
- Secretory breast carcinoma - ETV6-NTRK3.[5]
Others
- Congenital-infantile fibrosarcoma.[6]
- Cellular mesoblastic nephroma.[7][8]
- NTRK1 fusions occasionally in Glioblastoma (1-2%).[9]
Drugs
See also
References
- ↑ 1.0 1.1 Drilon, A.; Laetsch, TW.; Kummar, S.; DuBois, SG.; Lassen, UN.; Demetri, GD.; Nathenson, M.; Doebele, RC. et al. (02 2018). "Efficacy of Larotrectinib in TRK Fusion-Positive Cancers in Adults and Children.". N Engl J Med 378 (8): 731-739. doi:10.1056/NEJMoa1714448. PMID 29466156.
- ↑ "NTRK gene fusions as novel targets of cancer therapy across multiple tumour types". ESMO Open 1 (2): e000023. 2016. doi:10.1136/esmoopen-2015-000023. PMC 5070277. PMID 27843590. https://www.ncbi.nlm.nih.gov/pubmed/27843590.
- ↑ Hechtman, JF.; Benayed, R.; Hyman, DM.; Drilon, A.; Zehir, A.; Frosina, D.; Arcila, ME.; Dogan, S. et al. (Nov 2017). "Pan-Trk Immunohistochemistry Is an Efficient and Reliable Screen for the Detection of NTRK Fusions.". Am J Surg Pathol 41 (11): 1547-1551. doi:10.1097/PAS.0000000000000911. PMID 28719467.
- ↑ Lei, Y.; Chiosea, SI. (Jun 2012). "Re-evaluating historic cohort of salivary acinic cell carcinoma with new diagnostic tools.". Head Neck Pathol 6 (2): 166-70. doi:10.1007/s12105-011-0312-9. PMID 22127547.
- ↑ Vasudev, P.; Onuma, K. (Dec 2011). "Secretory breast carcinoma: unique, triple-negative carcinoma with a favorable prognosis and characteristic molecular expression.". Arch Pathol Lab Med 135 (12): 1606-10. doi:10.5858/arpa.2010-0351-RS. PMID 22129193.
- ↑ Sheng, WQ.; Hisaoka, M.; Okamoto, S.; Tanaka, A.; Meis-Kindblom, JM.; Kindblom, LG.; Ishida, T.; Nojima, T. et al. (Mar 2001). "Congenital-infantile fibrosarcoma. A clinicopathologic study of 10 cases and molecular detection of the ETV6-NTRK3 fusion transcripts using paraffin-embedded tissues.". Am J Clin Pathol 115 (3): 348-55. doi:10.1309/3H24-E7T7-V37G-AKKQ. PMID 11242790.
- ↑ Halalsheh, H.; McCarville, MB.; Neel, M.; Reynolds, M.; Cox, MC.; Pappo, AS. (Oct 2018). "Dramatic bone remodeling following larotrectinib administration for bone metastasis in a patient with TRK fusion congenital mesoblastic nephroma.". Pediatr Blood Cancer 65 (10): e27271. doi:10.1002/pbc.27271. PMID 29893456.
- ↑ Rudzinski, ER.; Lockwood, CM.; Stohr, BA.; Vargas, SO.; Sheridan, R.; Black, JO.; Rajaram, V.; Laetsch, TW. et al. (Jul 2018). "Pan-Trk Immunohistochemistry Identifies NTRK Rearrangements in Pediatric Mesenchymal Tumors.". Am J Surg Pathol 42 (7): 927-935. doi:10.1097/PAS.0000000000001062. PMID 29683818.
- ↑ Xu, T.; Wang, H.; Huang, X.; Li, W.; Huang, Q.; Yan, Y.; Chen, J. (Jun 2018). "Gene Fusion in Malignant Glioma: An Emerging Target for Next-Generation Personalized Treatment.". Transl Oncol 11 (3): 609-618. doi:10.1016/j.tranon.2018.02.020. PMID 29571074.
- ↑ Farago, AF.; Le, LP.; Zheng, Z.; Muzikansky, A.; Drilon, A.; Patel, M.; Bauer, TM.; Liu, SV. et al. (Dec 2015). "Durable Clinical Response to Entrectinib in NTRK1-Rearranged Non-Small Cell Lung Cancer.". J Thorac Oncol 10 (12): 1670-4. doi:10.1097/01.JTO.0000473485.38553.f0. PMID 26565381.