Kerbel Robert S
Sunnybrook Health Sciences Centre, Departments of Medical Biophysics and Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario M4N 3M5, Canada.
Science. 2006 May 26;312(5777):1171-5. doi: 10.1126/science.1125950.
For more than 50 years, a major goal of research in cancer therapeutics has been to develop universally effective agents that render cancer cells more sensitive to cytotoxic chemotherapy without substantially increasing toxicity to normal cells. The results of recent clinical trials indicate that certain antiangiogenic drugs may produce this long-sought effect. Here, I describe three distinct mechanisms that may help to explain the chemosensitizing activity of these drugs: normalizing tumor vasculature, preventing rapid tumor cell repopulation, and augmenting the antivascular effects of chemotherapy. I then discuss how these potential mechanisms might be exploited to maximize therapeutic efficacy.
五十多年来，癌症治疗研究的一个主要目标是开发普遍有效的药物，使癌细胞对细胞毒性化疗更敏感，同时又不会大幅增加对正常细胞的毒性。最近的临床试验结果表明，某些抗血管生成药物可能会产生这种长期寻求的效果。在此，我描述三种不同的机制，它们可能有助于解释这些药物的化学增敏活性：使肿瘤血管正常化、防止肿瘤细胞快速再增殖以及增强化疗的抗血管作用。然后，我将讨论如何利用这些潜在机制来最大化治疗效果。
