Ouali Kaïssa, Pellat Anna, Cohen Romain, Svrcek Magali, Penault-Llorca Frédérique, André Thierry
AP-HP, hôpital Saint-Antoine, service d'oncologie médicale, 75012 Paris, France.
AP-HP, hôpital Saint-Antoine, service d'oncologie médicale, 75012 Paris, France; Sorbonne université, Paris, France.
Bull Cancer. 2020 Apr;107(4):447-457. doi: 10.1016/j.bulcan.2019.11.014. Epub 2020 Feb 14.
The advent of molecular biology resulted in the discovery of new oncogenes that have led to the development of targeted therapies for the management of cancer patients. The development of these therapies has improved the prognosis of patients in various tumour localizations. The TRK receptor (tropomyosin receptor kinase) is a transmembrane receptor with a tyrosine kinase activity that plays a role in both cell proliferation and the physiology of the nervous system. Fusions involving the NTRK gene, which codes for this receptor, have been found in different types of solid tumours and lead to its constitutional activation. These fusions, however uncommon, are mainly found in rare pediatric tumours but can also be encountered in digestive cancers with high prevalence (such as colorectal cancer, especially in case of microsatellite instability, with a frequency of 2.5 to 38.5 %) or in aggressive cancers (such as pancreatic cancer). Therapies targeting TRK, such as larotrectinib or entrectinib, have shown significant response rates, usually greater than 6 months, for tumours from various primary sites presenting NTRK fusions and refractory to standard therapies. These fusions can be detected by different methods: immunohistochemistry, FISH (fluorescence in situ hybridization) as well as NGS (next generation sequencing). The intent of this review is to report on current knowledge on NTRK fusions in oncology and to discuss the role of these fusions in digestive cancers and potential therapeutic implications.
分子生物学的出现促使了新致癌基因的发现，这些基因推动了针对癌症患者治疗的靶向疗法的发展。这些疗法的发展改善了不同肿瘤部位患者的预后。TRK受体（原肌球蛋白受体激酶）是一种具有酪氨酸激酶活性的跨膜受体，在细胞增殖和神经系统生理过程中均发挥作用。编码该受体的NTRK基因发生的融合，已在不同类型的实体瘤中被发现，并导致其组成性激活。这些融合虽然不常见，但主要见于罕见的儿童肿瘤，不过在高发性消化系统癌症（如结直肠癌，尤其是微卫星不稳定的情况下，发生率为2.5%至38.5%）或侵袭性癌症（如胰腺癌）中也可能出现。针对TRK的疗法，如拉罗替尼或恩曲替尼，对于存在NTRK融合且对标准疗法耐药的各种原发部位肿瘤，已显示出显著的缓解率，通常超过6个月。这些融合可通过不同方法检测：免疫组织化学、荧光原位杂交（FISH）以及二代测序（NGS）。本综述旨在报告肿瘤学中关于NTRK融合的当前知识，并讨论这些融合在消化系统癌症中的作用及潜在治疗意义。
