ERK1/2 and p38α/β signaling in tumor cell quiescence: opportunities to control dormant residual disease.
ERK1/2 and p38α/β signaling in tumor cell quiescence: opportunities to control dormant residual disease.
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肿瘤细胞静脉中的ERK1/2和P38α/β信号传导：控制休眠残留疾病的机会。
DOI：
10.1158/1078-0432.ccr-10-2574
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发表时间：
2011-09-15
期刊：
影响因子：
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通讯作者：
Aguirre-Ghiso JA
中科院分区：
文献类型：
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作者：
Sosa MS;Avivar-Valderas A;Bragado P;Wen HC;Aguirre-Ghiso JA
原发性肿瘤治疗后的系统性微小残留病可保持数十年无症状。这被认为是由于不同器官中存在休眠的播散性肿瘤细胞（DTC）或微转移。滞留在脑、肺、肝和/或骨中的DTC是一个主要的临床问题，因为它们是转移的创始人，最终导致癌症患者死亡。由于我们对DTC生物学缺乏了解，这个问题进一步恶化。因此，几乎没有合理的治疗方法来防止休眠的DTC存活和扩展。几种癌症，包括黑色素瘤以及乳腺癌、前列腺癌和结肠直肠癌，在转移性复发发展之前经历休眠期。在此，我们回顾了我们在研究早期癌症进展、扩散和DTC休眠模型中ERK 1/2和p38α/β信号传导之间的相互作用方面的经验。我们还提供了这些发现的一些潜在的翻译和临床应用，并描述了一些目前使用的疗法可能有助于控制休眠疾病。最后，我们提请注意目前在不同疾病的临床试验中使用p38抑制剂，因为这些可能会加速转移的发展。
Systemic minimal residual disease after primary tumor treatment can remain asymptomatic for decades. This is thought to be due to the presence of dormant disseminated tumor cells (DTC) or micrometastases in different organs. DTCs lodged in brain, lungs, livers, and/or bone are a major clinical problem because they are the founders of metastasis, which ultimately kill cancer patients. The problem is further aggravated by our lack of understanding of DTC biology. In consequence, there are almost no rational therapies to prevent dormant DTCs from surviving and expanding. Several cancers, including melanoma as well as breast, prostate, and colorectal carcinomas, undergo dormant periods before metastatic recurrences develop. Here we review our experience in studying the cross-talk between ERK1/2 and p38α/β signaling in models of early cancer progression, dissemination, and DTC dormancy. We also provide some potential translational and clinical applications of these findings and describe how some currently used therapies might be useful to control dormant disease. Finally, we draw caution on the use of p38 inhibitors currently in clinical trials for different diseases as these may accelerate metastasis development.