Dormancy of metastatic melanoma.
Dormancy of metastatic melanoma.
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DOI：
10.1111/j.1755-148x.2009.00647.x
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发表时间：
2010-02
影响因子：
4.3
通讯作者：
Aguirre-Ghiso JA
中科院分区：
文献类型：
--
作者：
Ossowski L;Aguirre-Ghiso JA
黑色素瘤的转移休眠尚未受到足够的重视，很可能是因为一旦检测到转移，几乎总是致命的，并且可以理解的是，重点一直是寻找延长明显复发患者生命的方法。然而，对已发表的黑色素瘤临床和实验数据的分析表明，黑色素瘤生物学的某些方面模仿了最近与其他实体癌休眠相关的特征。其中一些黑色素瘤能够在原发性肿瘤进展过程中早期传播，并且一旦传播，可以多年不被发现（休眠）。皮肤黑色素瘤和葡萄膜黑色素瘤的比较表明，尽管它们具有相同的起源，但它们的临床进展却截然不同。对于本次讨论来说重要的是，40% 至 50% 的葡萄膜黑色素瘤在十多年的时间里仍未被发现，而不到 5% 的皮肤黑色素瘤表现出这种行为。两种类型的黑色素瘤都具有激活的癌基因突变，可提供自主的促增殖信号，但共识是这些不足以促进肿瘤进展。如果是这样的话，那么可以设想，无论癌基因突变如何，来自肿瘤细胞外部（微环境）的信号都会影响单个播散细胞的命运，使其进展或暂停在休眠状态。为了激发进一步的辩论和探究，我们在这里描述了一些可能改变播散细胞命运的潜在信号的例子，并简要描述了有关其他癌症休眠的当前知识。我们的希望是让读者相信，播散性黑色素瘤细胞确实会进入长期休眠期，找到诱导或延长休眠期的方法可能意味着黑色素瘤患者无症状寿命的延长。最终，了解休眠的生物学和休眠细胞存活的机制，可能有助于对它们进行特定的靶向和消除。
Metastatic dormancy of melanoma has not received sufficient attention, most likely because once detectable, metastasis is almost invariably fatal and, understandably, the focus has been on finding ways to prolong life of patients with overt recurrences. Nevertheless, analysis of the published clinical and experimental data on melanoma indicates that some aspect of melanoma biology imitate traits recently associated with dormancy in other solid cancers. Among them the ability of some melanomas to disseminate early during primary tumor progression and once disseminated, to remain undetected (dormant) for years. Comparison of cutaneous and uveal melanoma indicates that, in spite of being of the same origin, they differ profoundly in their clinical progression. Importantly for this discussion, between 40 and 50% of uveal melanoma remain undetected for longer than a decade, while less than 5% of cutaneous melanoma show this behavior. Both types of melanoma have activating oncogene mutations that provide autonomous pro-proliferative signals, yet the consensus is that those are not sufficient for tumor progression. If that is the case, it is possible to envision that signals from outside the tumor cell, (microenvironment) shape the fate of an individual disseminated cell, regardless of an oncogene mutation, to progress or to pause in a state of dormancy. To stimulate further debate and inquiry we describe here a few examples of potential signals that might modify the fate of disseminated cell and provide brief description of the current knowledge on dormancy in other cancers. Our hope is to convince the reader that disseminated melanoma cells do enter periods of prolonged dormancy and that finding ways to induce it, or to prolong it, might mean an extension of symptoms-free life for melanoma patients. Ultimately, understanding the biology of dormancy and the mechanisms of dormant cell survival, might allow for their specific targeting and elimination.