Chemotherapeutic resistance: surviving stressful situations.
Chemotherapeutic resistance: surviving stressful situations.
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DOI：
10.1158/0008-5472.can-11-0277
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发表时间：
2011-08-01
期刊：
影响因子：
11.2
通讯作者：
Hemann MT
中科院分区：
文献类型：
--
作者：
Gilbert LA;Hemann MT
化疗方案包括系统性地给予遗传毒性化合物，这些化合物通过成熟的DNA损伤反应信号网络诱导癌细胞死亡。对于肿瘤微环境中其他细胞类型的治疗如何影响治疗反应，人们知之甚少。在这里，我们讨论最近的工作，表明肿瘤邻近的细胞可以通过参与旁分泌程序来响应遗传毒性应激。虽然这种分泌反应在细胞应激条件下起到保护祖细胞和促进组织再生的作用，但它也可以被肿瘤细胞吸收以生存在一线化疗中。因此，局部促生存信号可能是基因毒性药物清除肿瘤的根本障碍，表明有效的治疗需要同时针对癌细胞和肿瘤微环境。
Chemotherapeutic regimens involve the systemic administration of genotoxic compounds that induce cancer cell death via well-established DNA damage response signaling networks. Less understood is how the treatment of other cell types within the tumor microenvironment impacts therapeutic response. Here we discuss recent work that shows that tumor-adjacent cells can respond to genotoxic stress by engaging a paracrine secretory program. While this secretory response serves to protect progenitor cells and promote tissue regeneration in conditions of cellular stress, it can also be coopted by tumor cells to survive front-line chemotherapy. Thus, local pro-survival signaling may present a fundamental barrier to tumor clearance by genotoxic agents, suggesting that effective treatments need to target both cancer cells and the tumor microenvironment.