Reengineering the Tumor Microenvironment to Alleviate Hypoxia and Overcome Cancer Heterogeneity.
Reengineering the Tumor Microenvironment to Alleviate Hypoxia and Overcome Cancer Heterogeneity.
复制标题
DOI：
10.1101/cshperspect.a027094
复制
发表时间：
2016-12-01
影响因子：
5.4
通讯作者：
Jain RK
中科院分区：
文献类型：
--
作者：
Martin JD;Fukumura D;Duda DG;Boucher Y;Jain RK
实体肿瘤由癌细胞和间质细胞组成，包括驻留和过渡的免疫细胞--它们都存在于细胞外基质(ECM)中--由血管滋养，由淋巴管排出。微环境成分在形态、表型和生理上存在异常和异质性。这种异常包括由泄漏和受压的血管组成的低效肿瘤血管网络，这损害了血液流动和氧气输送。某些肿瘤区域的低氧-或局灶性缺氧-是癌症进展、转移、免疫抑制和治疗耐药的中介因素。因此，修复异常和异质的微环境--特别是缺氧--可以显著改善实体肿瘤的治疗。在这里，我们总结了两种重组肿瘤微环境(TME)的策略-血管正常化和减压-可以缓解缺氧。此外，我们还讨论了这两种策略单独以及相互结合--或其他治疗策略--如何克服癌症异质性带来的挑战。
Solid tumors consist of cancer cells and stromal cells, including resident and transiting immune cells—all ensconced in an extracellular matrix (ECM)—nourished by blood vessels and drained by lymphatic vessels. The microenvironment constituents are abnormal and heterogeneous in morphology, phenotype, and physiology. Such irregularities include an inefficient tumor vascular network comprised of leaky and compressed vessels, which impair blood flow and oxygen delivery. Low oxygenation in certain tumor regions—or focal hypoxia—is a mediator of cancer progression, metastasis, immunosuppression, and treatment resistance. Thus, repairing an abnormal and heterogeneous microenvironment—and hypoxia in particular—can significantly improve treatments of solid tumors. Here, we summarize two strategies to reengineer the tumor microenvironment (TME)—vessel normalization and decompression—that can alleviate hypoxia. In addition, we discuss how these two strategies alone and in combination with each other—or other therapeutic strategies—may overcome the challenges posed by cancer heterogeneity.
登录
查看更多内容
影响因子：
--
作者：
Bredfeldt JS;Liu Y;Conklin MW;Keely PJ;Mackie TR;Eliceiri KW
通讯作者：
Eliceiri KW
影响因子：
2.6
作者：
BROWN, JM
通讯作者：
BROWN, JM
影响因子：
11.2
作者：
Arjaans, Marlous;Munnink, Thijs H. Oude;de Vries, Elisabeth G. E.
通讯作者：
de Vries, Elisabeth G. E.
影响因子：
6.4
作者：
Auvinen, Paivi;Tammi, Raija;Tammi, Markku
通讯作者：
Tammi, Markku
影响因子：
64.8
作者：
Bedard PL;Hansen AR;Ratain MJ;Siu LL
通讯作者：
Siu LL