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- W2809131968 abstract "Oncogenes derived from the neurotrophin receptor tropomyosin-related kinase TrkA act as drivers in sub-populations of a wide-range of human cancers. This, combined with a recent report that both adult and childhood cancers driven by novel oncogenic TrkA chimeric-fusions exhibit profound, long-lived therapeutic responses to the Trk inhibitor Larotrectinib, highlights the need to improve clinical detection of TrkA oncogene-driven cancers in order to maximise this novel therapeutic potential. Cancers potentially driven by TrkA oncogenes include a proportion of paediatric neuroblastomas (NBs) that express the alternative TrkA splice variant TrkAIII, which exhibits exon 6, 7 and 9 skipping and oncogenic-activity that depends upon deletion of the extracellular D4 Ig-like domain. In contrast to fully spliced TrkA, which exhibits tumour suppressor activity in NB and associates with good prognosis, TrkAIII associates with advanced stage metastatic disease, post therapeutic relapse and worse prognosis, induces malignant transformation of NIH-3T3 cells and exhibits oncogenic activity in NB models. TrkAIII induction in NB cells is stress-regulated by conditions that mimic hypoxia or perturbate the ER with potential to change TrkA tumour-suppressing signals into oncogenic TrkAIII signals within the stressful tumour microenvironment. In contrast to cell surface TrkA, TrkAIII re-localises to intracellular pre-Golgi membranes, centrosomes and mitochondria, within which it exhibits spontaneous ligand-independent activation, triggering a variety of mechanisms that promote tumorigenicity and malignant behaviour, which impact the majority of cancer hallmarks. In this review, we present updates on TrkAIII detection and association with human malignancies, the multiple ways TrkAIII exerts oncogenic activity and potential therapeutic approaches for TrkAIII expressing cancers, with particular reference to NB." @default.
- W2809131968 created "2018-06-29" @default.
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- W2809131968 date "2018-06-18" @default.
- W2809131968 modified "2023-10-15" @default.
- W2809131968 title "The oncogenic neurotrophin receptor tropomyosin-related kinase variant, TrkAIII" @default.
- W2809131968 cites W1551283376 @default.
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- W2809131968 cites W1971988052 @default.
- W2809131968 cites W1972746043 @default.
- W2809131968 cites W1973354681 @default.
- W2809131968 cites W1975685675 @default.
- W2809131968 cites W1979188008 @default.
- W2809131968 cites W1996277017 @default.
- W2809131968 cites W2010178708 @default.
- W2809131968 cites W2010978319 @default.
- W2809131968 cites W2019255889 @default.
- W2809131968 cites W2026588006 @default.
- W2809131968 cites W2032511198 @default.
- W2809131968 cites W2034291076 @default.
- W2809131968 cites W2035453171 @default.
- W2809131968 cites W2035897513 @default.
- W2809131968 cites W2038075932 @default.
- W2809131968 cites W2038633902 @default.
- W2809131968 cites W2038648190 @default.
- W2809131968 cites W203888263 @default.
- W2809131968 cites W2041094651 @default.
- W2809131968 cites W2043001906 @default.
- W2809131968 cites W2055343221 @default.
- W2809131968 cites W2056056877 @default.
- W2809131968 cites W2063423211 @default.
- W2809131968 cites W2064378491 @default.
- W2809131968 cites W2071409339 @default.
- W2809131968 cites W2075009035 @default.
- W2809131968 cites W2082423911 @default.
- W2809131968 cites W2084235441 @default.
- W2809131968 cites W2091309613 @default.
- W2809131968 cites W2092692114 @default.
- W2809131968 cites W2096388436 @default.
- W2809131968 cites W2098752829 @default.
- W2809131968 cites W2100175873 @default.
- W2809131968 cites W2103116338 @default.
- W2809131968 cites W2109269285 @default.
- W2809131968 cites W2113148252 @default.
- W2809131968 cites W2117692326 @default.
- W2809131968 cites W2118010975 @default.
- W2809131968 cites W2120308617 @default.
- W2809131968 cites W2132616450 @default.
- W2809131968 cites W2138605089 @default.
- W2809131968 cites W2144814885 @default.
- W2809131968 cites W2163299200 @default.
- W2809131968 cites W2166859762 @default.
- W2809131968 cites W2167755204 @default.
- W2809131968 cites W2167889216 @default.
- W2809131968 cites W2169518540 @default.
- W2809131968 cites W2174095318 @default.
- W2809131968 cites W2223535266 @default.
- W2809131968 cites W2249356557 @default.
- W2809131968 cites W2279591321 @default.
- W2809131968 cites W2295053346 @default.
- W2809131968 cites W2335155752 @default.
- W2809131968 cites W2506019455 @default.
- W2809131968 cites W2547074420 @default.
- W2809131968 cites W2559805899 @default.
- W2809131968 cites W2581718522 @default.
- W2809131968 cites W2590195415 @default.
- W2809131968 cites W2594299422 @default.
- W2809131968 cites W2595953303 @default.
- W2809131968 cites W2608026191 @default.
- W2809131968 cites W2616954162 @default.
- W2809131968 cites W2620490360 @default.
- W2809131968 cites W2720029603 @default.
- W2809131968 cites W2753709413 @default.
- W2809131968 cites W2759551874 @default.
- W2809131968 cites W2765263172 @default.
- W2809131968 cites W2771985353 @default.
- W2809131968 cites W2780009084 @default.
- W2809131968 cites W2782468867 @default.
- W2809131968 cites W2783667606 @default.
- W2809131968 cites W2789281724 @default.
- W2809131968 cites W2790254562 @default.
- W2809131968 cites W2795693351 @default.
- W2809131968 cites W2982817004 @default.
- W2809131968 cites W3171748570 @default.
- W2809131968 cites W4231536927 @default.
- W2809131968 cites W4231919180 @default.
- W2809131968 cites W4292604187 @default.
- W2809131968 doi "https://doi.org/10.1186/s13046-018-0786-3" @default.
- W2809131968 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6006588" @default.
- W2809131968 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/29914559" @default.
- W2809131968 hasPublicationYear "2018" @default.
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