Reengineering the Tumor Vasculature: Improving Drug Delivery and Efficacy.
Reengineering the Tumor Vasculature: Improving Drug Delivery and Efficacy.
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DOI：
10.1016/j.trecan.2018.02.010
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发表时间：
2018-04
期刊：
影响因子：
18.4
通讯作者：
Jain RK
中科院分区：
文献类型：
--
作者：
Stylianopoulos T;Munn LL;Jain RK
实体瘤就像一个异常器官，由癌细胞和嵌入细胞外基质的各种宿主细胞组成，由血管滋养并由淋巴管排出。在从血流到癌细胞的旅程中，治疗剂必须穿过血管壁和癌细胞所在的细胞外基质。肿瘤在有限空间中的生长以及基质成分（包括胶原蛋白（黄色）和透明质酸（粉色））的沉积，会增加“固体应力”，从而压缩血液和淋巴管并损害其功能。肿瘤血管的渗漏还会损害肿瘤血流并增加“肿瘤内流体压力”。异常的血流不仅阻碍药物输送，而且由此产生的缺氧也会促进肿瘤的侵袭、转移、免疫抑制、炎症、纤维化和治疗抵抗。工程师和物理科学家剖析了这些异常背后的分子、细胞和物理机制，并制定了许多策略来重新设计肿瘤微环境以克服这些障碍，从而改善治疗的实施和疗效。最后，这些策略已从实验室转移到临床用于癌症治疗，并有可能改善许多以异常微环境为特征的疾病的治疗结果。
A solid tumor is like an aberrant organ – comprised of cancer cells and a variety of host cells embedded in an extracellular matrix – nourished by blood vessels and drained by lymphatic vessels. In its journey from the blood stream to cancer cells, a therapeutic agent must cross the vessel wall and the extracellular matrix that cancer cells are ensconced in. Growth of tumors in a confined space along with deposition of matrix components, including collagen (yellow) and hyaluronan (pink), increases ‘solid stress’, which compresses blood and lymphatic vessels and impairs their function. The leakiness of tumor vessels also impairs tumor blood flow and increases ‘intratumor fluid pressure’. The abnormal blood flow not only impedes drug delivery, but the resulting hypoxia also aids tumor invasion, metastasis, immunosuppression, in flammation, fibrosis, and treatment resistance. Engineers and physical scientists have dissected the molecular, cellular, and physical mechanisms underlying these abnormalities and developed a number of strategies to reengineer the tumor microenvironment to overcome these barriers and thus improve delivery and efficacy of treatments. Finally, these strategies have been translated from bench to bedside for treatment of cancer and have the potential to improve the treatment outcome for many diseases characterized by an abnormal microenvironment.
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影响因子：
17.1
作者：
Pinter M;Jain RK
通讯作者：
Jain RK
DOI：
10.1038/nrc.2017.83
发表时间：
2017-11
期刊：
Nature reviews. Cancer
影响因子：
--
作者：
Mitchell MJ;Jain RK;Langer R
通讯作者：
Langer R
影响因子：
28.2
作者：
Incio J;Liu H;Suboj P;Chin SM;Chen IX;Pinter M;Ng MR;Nia HT;Grahovac J;Kao S;Babykutty S;Huang Y;Jung K;Rahbari NN;Han X;Chauhan VP;Martin JD;Kahn J;Huang P;Desphande V;Michaelson J;Michelakos TP;Ferrone CR;Soares R;Boucher Y;Fukumura D;Jain RK
通讯作者：
Jain RK
影响因子：
50.3
作者：
Jain RK
通讯作者：
Jain RK
DOI：
10.1073/pnas.1213353109
发表时间：
2012-09-18
影响因子：
11.1
作者：
Stylianopoulos, Triantafyllos;Martin, John D.;Jain, Rakesh K.
通讯作者：
Jain, Rakesh K.