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癌症的单克隆抗体疗法。

Monoclonal antibody therapy of cancer.

作者信息

Adams Gregory P, Weiner Louis M

机构信息

Department of Medical Oncology, Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, Pennsylvania 19111, USA.

出版信息

Nat Biotechnol. 2005 Sep;23(9):1147-57. doi: 10.1038/nbt1137.

Abstract

The most significant recent advances in the application of monoclonal antibodies (mAbs) to oncology have been the introduction and approval of bevacizumab (Avastin), an anti-vascular endothelial growth factor antibody, and of cetuximab (Erbitux), an anti-epidermal growth factor antibody. In combination with standard chemotherapy regimens, bevacizumab significantly prolongs the survival of patients with metastatic cancers of the colorectum, breast and lung. Cetuximab, used alone or with salvage chemotherapy, produces clinically meaningful anti-tumor responses in patients with chemotherapy-refractory cancers of the colon and rectum. In addition, the anti-HER2/neu antibody trastuzumab (Herceptin), in combination with standard adjuvant chemotherapy, has been shown to reduce relapses and prolong disease-free and overall survival in high-risk patients after definitive local therapy for breast cancer. These exciting recent results provide optimism for the development of mAbs that bind novel targets, exploit novel mechanisms of action or possess improved tumor targeting. Progress in the clinical use of radioimmunoconjugates remains hindered by complexity of administration, toxicity concerns and insufficiently selective tumor targeting.

摘要

单克隆抗体(mAb)在肿瘤学应用方面最近取得的最重大进展是抗血管内皮生长因子抗体贝伐单抗(阿瓦斯汀)和抗表皮生长因子抗体西妥昔单抗(爱必妥)的引入和获批。与标准化疗方案联合使用时,贝伐单抗可显著延长患有结直肠癌、乳腺癌和肺癌的转移性癌症患者的生存期。西妥昔单抗单独使用或与挽救性化疗联合使用,可在患有化疗难治性结肠癌和直肠癌的患者中产生具有临床意义的抗肿瘤反应。此外,抗HER2/neu抗体曲妥珠单抗(赫赛汀)与标准辅助化疗联合使用,已被证明可减少乳腺癌明确局部治疗后高危患者的复发,并延长无病生存期和总生存期。这些近期令人振奋的结果为开发结合新靶点、利用新作用机制或具有更好肿瘤靶向性的单克隆抗体带来了希望。放射免疫缀合物临床应用的进展仍然受到给药复杂性、毒性问题以及肿瘤靶向选择性不足的阻碍。

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