Tropomyosin-related kinase B/brain derived-neurotrophic factor signaling pathway as a potential therapeutic target for colorectal cancer
Tropomyosin-related kinase B/brain derived-neurotrophic factor signaling pathway as a potential therapeutic target for colorectal cancer
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DOI：
10.3748/wjg.v22.i2.490
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发表时间：
2016-01-14
影响因子：
4.3
通讯作者：
Mathonnet, Muriel
中科院分区：
文献类型：
--
作者：
Akil, Hussein;Perraud, Aurelie;Mathonnet, Muriel
结直肠癌（CRC）是西方国家癌症相关死亡的第二大常见原因。大约四分之一的新诊断的CRC患者有转移，另外40%-50%的患者在所有标准治疗后经历疾病复发或发生转移。因此，了解参与CRC进展的分子机制并随后开发新的治疗靶点对于改善CRC的管理和患者的长期生存至关重要。几种酪氨酸激酶受体与CRC的发生、进展和转移有关，包括表皮生长因子受体（EGFR）和血管EGFR。近年来，原肌球蛋白相关激酶B（Trk B）作为一种酪氨酸激酶受体，在大肠癌中被发现具有明显的生物学和临床特征，如肿瘤细胞的生长和存活、转移形成和预后不良。现就TrkB及其配体脑源性神经营养因子在结直肠癌中的意义作一综述。我们专注于它们在CRC肿瘤样本中的表达，以及它们在CRC细胞系和体内模型中的功能作用。最后，我们讨论了治疗方法，可以导致新的治疗药物的发展，用于治疗表达TrkB的CRC肿瘤。
Colorectal cancer (CRC) is the second most common cause of cancer-related death in western countries. Approximately one-quarter of newly diagnosed patients for CRC have metastases, and a further 40%-50% experience disease recurrence or develop metastases after all standard therapies. Therefore, understanding the molecular mechanisms involved in the progression of CRC and subsequently developing novel therapeutic targets is crucial to improve management of CRC and patients' long-term survival. Several tyrosine kinase receptors have been implicated in CRC development, progression and metastasis, including epidermal growth factor receptor (EGFR) and vascular EGFR. Recently, tropomyosin-related kinase B (TrkB), a tyrosine kinase receptor, has been reported in CRC and found to clearly exert several biological and clinical features, such as tumor cell growth and survival in vitro and in vivo, metastasis formation and poor prognosis. Here we review the significance of TrkB and its ligand brain derived-neurotrophic factor in CRC. We focus on their expression in CRC tumor samples, and their functional roles in CRC cell lines and in in vivo models. Finally we discuss therapeutic approaches that can lead to the development of novel therapeutic agents for treating TrkB-expressing CRC tumors.