为什么要将黑色素瘤中的肿瘤基质作为靶点？
Why target the tumor stroma in melanoma?
作者信息
Hutchenreuther James, Leask Andrew
机构信息
Departments of Physiology and Pharamacology and Dentistry, University of Western Ontario, London, ON, N6A 5C1, Canada.
出版信息
J Cell Commun Signal. 2018 Mar;12(1):113-118. doi: 10.1007/s12079-017-0419-1. Epub 2017 Nov 6.
Abstract
Melanoma metastasis is fatal. Melanoma cells are often characterized by an activated extracellular signal-regulated kinase (ERK) pathway downstream of mutations in BRAF. Therapies targeting these BRAF mutations are useful for a while; however, patients ultimately develop resistance to these therapies. Recent evidence suggests that this resistance occurs when tumor cells leave their microenvironment and migrate on a stiff, activated tumor stroma; that is, this resistance is linked to the presence of an extracellular matrix reminiscent of a fibrotic micronvironment. These data suggest that agents targeting fibrosis might be used to treat melanoma. We therefore discuss what is known about the tumor stroma in melanoma. An emergent target, CCN2 (CTGF), that is required for fibrosis, may also be a good target for drug-resistant melanoma. Intriguingly, anti-CCN2 antibodies are currently under clinical development.
摘要
黑色素瘤转移是致命的。黑色素瘤细胞的特征通常是BRAF基因发生突变后，细胞外信号调节激酶（ERK）通路被激活。针对这些BRAF突变的疗法在一段时间内是有效的；然而，患者最终会对这些疗法产生耐药性。最近的证据表明，当肿瘤细胞离开其微环境并在僵硬、活化的肿瘤基质上迁移时，就会出现这种耐药性；也就是说，这种耐药性与类似于纤维化微环境的细胞外基质的存在有关。这些数据表明，靶向纤维化的药物可能用于治疗黑色素瘤。因此，我们讨论一下关于黑色素瘤肿瘤基质的已知情况。一种新兴的靶点CCN2（结缔组织生长因子）是纤维化所必需的，它也可能是耐药黑色素瘤的一个良好靶点。有趣的是，抗CCN2抗体目前正在进行临床试验。
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