Tackling the tumor microenvironment: what challenge does it pose to anticancer therapies?
Tackling the tumor microenvironment: what challenge does it pose to anticancer therapies?
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DOI：
10.1007/s13238-014-0097-1
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发表时间：
2014-11
期刊：
影响因子：
21.1
通讯作者：
Sun Y
中科院分区：
文献类型：
--
作者：
Chen F;Qi X;Qian M;Dai Y;Sun Y
癌症是一种高度侵袭性和破坏性的疾病，治愈的障碍不仅仅来自癌症本身。靶向治疗很难实现，因为大多数癌症比想象的要复杂得多。包括化疗和放射治疗在内的主流方法作为常规的临床方案经常失败，最终导致难以治愈的病理。一个主要原因是在多次给药期间，存活的癌细胞逐渐迅速地重新繁殖。新的应激反应分子通路越来越多地被发现，并显示出作为先进策略的新兴靶点的前景，这些先进策略既针对从头开始，也针对获得性抗性。我们重点介绍了最近的数据报道，治疗，特别是那些基因毒性的治疗，可以在肿瘤微环境(TMEN)的非癌症成分中诱导高度保守的损伤反应。包括但不限于核因子-kB和C/eBP-β在内的主要调控因子参与其中，它们的信号级联最终导致一个强大的、长期的和全基因组的分泌程序，形成一个激活的TTMEN，释放大量的可溶性因子。宿主基质的损伤诱导但本质上偏离靶点和细胞的非自主分泌表型会导致不良后果，其中之一是癌细胞的获得性耐药。利用来自TMEN的信号，这是一个经常被医疗干预破坏的病理生理学利基，如果将适当的行动巧妙地整合到现代治疗中，就有可能提高整体疗效和改善临床结果。因此，抗癌方案应该得到很好的调整，以建立一条创新的临床途径，这种进步将使未来的肿瘤学治疗更加特异、准确、彻底和个性化。
Cancer is a highly aggressive and devastating disease, and impediments to a cure arise not just from cancer itself. Targeted therapies are difficult to achieve since the majority of cancers are more intricate than ever imagined. Mainstream methodologies including chemotherapy and radiotherapy as routine clinical regimens frequently fail, eventually leading to pathologies that are refractory and incurable. One major cause is the gradual to rapid repopulation of surviving cancer cells during intervals of multiple-dose administration. Novel stress-responsive molecular pathways are increasingly unmasked and show promise as emerging targets for advanced strategies that aim at both de novo and acquired resistance. We highlight recent data reporting that treatments particularly those genotoxic can induce highly conserved damage responses in non-cancerous constituents of the tumor microenvironment (TMEN). Master regulators, including but not limited to NF-kB and C/EBP-β, are implicated and their signal cascades culminate in a robust, chronic and genome-wide secretory program, forming an activated TMEN that releases a myriad of soluble factors. The damage-elicited but essentially off target and cell non-autonomous secretory phenotype of host stroma causes adverse consequences, among which is acquired resistance of cancer cells. Harnessing signals arising from the TMEN, a pathophysiological niche frequently damaged by medical interventions, has the potential to promote overall efficacy and improve clinical outcomes provided that appropriate actions are ingeniously integrated into contemporary therapies. Thereby, anticancer regimens should be well tuned to establish an innovative clinical avenue, and such advancement will allow future oncological treatments to be more specific, accurate, thorough and personalized.
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影响因子：
78.5
作者：
Collado, Manuel;Serrano, Manuel
通讯作者：
Serrano, Manuel
影响因子：
13.6
作者：
Freund A;Orjalo AV;Desprez PY;Campisi J
通讯作者：
Campisi J
DOI：
10.1146/annurev-pathol-121808-102144
发表时间：
2010
期刊：
Annual review of pathology
影响因子：
--
作者：
Coppé JP;Desprez PY;Krtolica A;Campisi J
通讯作者：
Campisi J
影响因子：
7.5
作者：
Chandler, Hollie;Peters, Gordon
通讯作者：
Peters, Gordon
影响因子：
10.5
作者：
Chien, Yuchen;Scuoppo, Claudio;Lowe, Scott W.
通讯作者：
Lowe, Scott W.