Resistance to Anti-Angiogenic Therapy in Cancer-Alterations to Anti-VEGF Pathway.

Resistance to Anti-Angiogenic Therapy in Cancer-Alterations to Anti-VEGF Pathway.
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DOI:
10.3390/ijms19041232
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发表时间:
2018-04-18
影响因子:
5.6
通讯作者:
Sakai Y
Sakai Y
中科院分区:
生物学2区
文献类型:
--
作者:
Itatani Y;Kawada K;Yamamoto T;Sakai Y

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抗血管生成治疗是许多类型的实体癌的有前途的策略之一。贝伐单抗(Avastin)是一种重组人源化血管内皮生长因子(VEGF)A单克隆抗体,2004年首次被美国食品药品监督管理局(FDA)批准作为抗血管生成药物用于治疗转移性结直肠癌(CRC)。此外,其他VEGF途径抑制剂,包括小分子酪氨酸激酶抑制剂(舒尼替尼、索拉非尼和帕唑帕尼)、可溶性VEGF诱饵受体(阿柏西普)和VEGF受体2(VEGFR2)的人源化单克隆抗体(雷莫芦单抗)已被批准用于癌症治疗。虽然许多类型的VEGF通路抑制剂可以改善大多数癌症患者的生存率,但有些患者几乎没有或没有受益。对包括抗VEGF抑制剂在内的许多肿瘤药物的原发性或获得性耐药性是癌症治疗中的常见问题。本文综述了VEGF途径以外的血管生成机制。这些机制参与了癌症患者对抗VEGF疗法的耐药性的发展。
Anti-angiogenic therapy is one of the promising strategies for many types of solid cancers. Bevacizumab (Avastin), a recombinant humanized monoclonal antibody of vascular endothelial growth factor (VEGF) A, was approved for the first time as an anti-angiogenic drug for the treatment of metastatic colorectal cancer (CRC) by the Food and Drug Administration (FDA) in 2004. In addition, the other VEGF pathway inhibitors including small molecule tyrosine kinase inhibitors (sunitinib, sorafenib, and pazopanib), a soluble VEGF decoy receptor (aflibercept), and a humanized monoclonal antibody of VEGF receptor 2 (VEGFR2) (ramucirumab) have been approved for cancer therapy. Although many types of VEGF pathway inhibitors can improve survival in most cancer patients, some patients have little or no beneficial effect from them. The primary or acquired resistance towards many oncological drugs, including anti-VEGF inhibitors, is a common problem in cancer treatment. This review summarizes the proposed alternative mechanisms of angiogenesis other than the VEGF pathway. These mechanisms are involved in the development of resistance to anti-VEGF therapies in cancer patients.
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