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一种新型多酪氨酸激酶靶向药物——卡博替尼,用于探索抗血管生成疗法治疗多种实体瘤的未来前景。

A novel multiple tyrosine-kinase targeted agent to explore the future perspectives of anti-angiogenic therapy for the treatment of multiple solid tumors: cabozantinib.

作者信息

Roy Subhajit, Narang Bawneet K, Rastogi Shiva K, Rawal Ravindra K

机构信息

Department of Pharmaceutical Chemistry, Indo-Soviet Friendship College of Pharmacy, Ferozepur Road, Ghal Kalan, Moga-142 001, Punjab, India.

出版信息

Anticancer Agents Med Chem. 2015;15(1):37-47. doi: 10.2174/1871520614666140902153840.

Abstract

The process of angiogenesis involves the formation of new blood vessels from pre-existing vasculature by the over expression of certain factors leading to the growth and development of all solid tumor types. Hepatocyte growth factor receptor abbreviated as c-Met and vascular endothelial growth factor abbreviated as VEGF are some of the factors responsible for the induction in tumor growth and development. Recently a number of analogues associated with these receptors are under study. US FDA on November 29, 2012 approved a drug named cabozantinib formerly known as XL184 which is being marketed under the trade name of Cometriq for the treatment of Medullary Thyroid Cancer (MTC). Designing of the drug has been done in such a fashion that it can inhibit both VEGFR2 and c-Met simultaneously without over expressing any of the factors leading to the inhibition of angiogenesis. The drug is still under study for the evaluation of its efficacy in cases of many other solid tumor types including breast cancer, castration resistant prostate cancer (CRPC), renal cell carcinoma (RCC), hepatocellular carcinoma (HCC), gastric or gastroesophageal junction cancer, melanoma, small cell lung cancer (SCLC), ovarian cancer and primary peritoneal or fallopian tube carcinoma. This review article consists of preclinical and clinical data of cabozantinib and its efficacy and safety towards various types of solid tumors.

摘要

血管生成过程涉及从已有的脉管系统形成新血管,这是由某些因子的过度表达导致的,这些因子会促使所有实体瘤类型生长和发展。肝细胞生长因子受体简称为c-Met,血管内皮生长因子简称为VEGF,它们是诱导肿瘤生长和发展的部分因子。最近,一些与这些受体相关的类似物正在研究中。美国食品药品监督管理局于2012年11月29日批准了一种名为卡博替尼(曾用名XL184)的药物,该药物以Cometriq为商品名销售,用于治疗甲状腺髓样癌(MTC)。该药物的设计方式使其能够同时抑制VEGFR2和c-Met,而不会过度表达任何导致血管生成抑制的因子。该药物仍在研究中,以评估其在包括乳腺癌、去势抵抗性前列腺癌(CRPC)、肾细胞癌(RCC)、肝细胞癌(HCC)、胃癌或胃食管交界癌、黑色素瘤、小细胞肺癌(SCLC)、卵巢癌以及原发性腹膜或输卵管癌等多种其他实体瘤类型病例中的疗效。这篇综述文章包含了卡博替尼的临床前和临床数据,以及它对各种实体瘤的疗效和安全性。

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