Targeting tumour microenvironment by tyrosine kinase inhibitor.
Targeting tumour microenvironment by tyrosine kinase inhibitor.
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通过酪氨酸激酶抑制剂靶向肿瘤微环境
DOI：
10.1186/s12943-018-0800-6
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发表时间：
2018-02-19
期刊：
影响因子：
37.3
通讯作者：
Cheng YC
中科院分区：
文献类型：
--
作者：
Tan HY;Wang N;Lam W;Guo W;Feng Y;Cheng YC
肿瘤微环境（TME）是肿瘤生长和转移的关键决定因素。TME对于每种类型和位置的肿瘤可能非常不同，并且TME在肿瘤生长期间可能不断变化。周围微环境中的多个对应物包括间充质、造血来源的细胞以及非细胞组分影响TME。因此，应该进一步探索可以破坏有利于肿瘤的微环境的治疗方法用于癌症治疗。以前的努力在解开TME组件的失调机制已经确定了许多蛋白酪氨酸激酶，而其相应的抑制剂已被证明对TME的有效调节作用。最近的工作已经证明，除了对癌细胞的直接作用之外，酪氨酸激酶抑制剂（TKI）已经涉及导致癌症消退的失调的TME组分的失活或正常化。无论是通过重新致敏肿瘤细胞还是逆转免疫耐受微环境，TKI的这些TME调节机制的出现支持TKI与当前化疗或免疫疗法联合用于癌症治疗。因此，正确理解TKI对TME的调节作用可能为TKI治疗癌症提供另一种作用模式。本文综述了TME组分中激酶激活或旁分泌配体产生的模式，并总结了各种TKI在调节TME组分方面的潜在用途。最后，从有效性和安全性的角度讨论了当前TKI与免疫治疗的联合使用。
Tumour microenvironment (TME) is a key determinant of tumour growth and metastasis. TME could be very different for each type and location of tumour and TME may change constantly during tumour growth. Multiple counterparts in surrounding microenvironment including mesenchymal-, hematopoietic-originated cells as well as non-cellular components affect TME. Thus, therapeutics that can disrupt the tumour-favouring microenvironment should be further explored for cancer therapy. Previous efforts in unravelling the dysregulated mechanisms of TME components has identified numerous protein tyrosine kinases, while its corresponding inhibitors have demonstrated potent modulatory effect on TME. Recent works have demonstrated that beyond the direct action on cancer cells, tyrosine kinase inhibitors (TKIs) have been implicated in inactivation or normalization of dysregulated TME components leading to cancer regression. Either through re-sensitizing the tumour cells or reversing the immunological tolerance microenvironment, the emergence of these TME modulatory mechanism of TKIs supports the combinatory use of TKIs with current chemotherapy or immunotherapy for cancer therapy. Therefore, an appropriate understanding on TME modulation by TKIs may offer another mode of action of TKIs for cancer treatment. This review highlights mode of kinase activation or paracrine ligand production from TME components and summarises the findings on the potential use of various TKIs on regulating TME components. At last, the combination use of current TKIs with immunotherapy in the perspectives of efficacy and safety are discussed.
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表皮生长因子受体抑制通过血管正常化调节微环境，从而提高化疗和放疗疗效。
影响因子：
3.7
作者：
Cerniglia, George J.;Pore, Nabendu;Tsai, Jeff H.;Schultz, Susan;Mick, Rosemarie;Choe, Regine;Xing, Xiaoman;Durduran, Turgut;Yodh, Arjun G.;Evans, Sydney M.;Koch, Cameron J.;Hahn, Stephen M.;Quon, Harry;Sehgal, Chandra M.;Lee, William M. F.;Maity, Amit
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影响因子：
2.2
作者：
Bose A;Lowe DB;Rao A;Storkus WJ
通讯作者：
Storkus WJ
DOI：
10.1158/1541-7786.mcr-08-0169
发表时间：
2008-11
期刊：
Molecular cancer research : MCR
影响因子：
--
作者：
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通讯作者：
Jove R
影响因子：
3.8
作者：
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通讯作者：
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影响因子：
4.8
作者：
Bhattacharjee, Ashish;Pal, Srabani;Cathcart, Martha K.
通讯作者：
Cathcart, Martha K.