Cross Cancer Institute, Department of Medical Oncology, 11560 University Avenue, Edmonton, Alberta, Canada.
Expert Opin Biol Ther. 2011 Mar;11(3):405-13. doi: 10.1517/14712598.2011.557657. Epub 2011 Feb 1.
Angiogenesis is a key factor in the development of aberrant blood vessels required for malignant growth, invasion and progression. Inhibiting VEGF is by far the most clinically advanced anti-angiogenic target. Bevacizumab (BV), the only humanized mAb directed against VEGF, is approved for use in multiple tumor types after successful clinical trial results demonstrated benefits in progression-free survival and/or overall survival when combined with common cytotoxic chemotherapies.
The review focuses on the use of BV in colorectal cancer, discusses the clinical trial data supporting its increasing use and explores its limitations. Readers will gain a succinct description of the trial data demonstrating a modest survival benefit in metastatic colorectal cancer (mCRC) and the lack of benefit of BV when utilized in the adjuvant setting. A review of common BV toxicities and a discussion about possible BV resistance mechanisms are also provided.
Although BV has demonstrated efficacy in mCRC, there is an urgent need to improve the understanding of its mechanism of action and the development of BV resistance. Furthermore, there is a need for delineating predictive markers of BV efficacy and toxicity.
血管生成是恶性生长、浸润和进展所必需的异常血管形成的关键因素。到目前为止，抑制 VEGF 是最具临床先进的抗血管生成靶点。贝伐单抗（BV）是唯一针对 VEGF 的人源化单克隆抗体，在成功的临床试验结果表明与常见细胞毒性化疗联合使用在无进展生存期和/或总生存期方面具有获益后，已被批准用于多种肿瘤类型。
本综述重点讨论了 BV 在结直肠癌中的应用，讨论了支持其广泛应用的临床试验数据，并探讨了其局限性。读者将简要了解在转移性结直肠癌（mCRC）中具有适度生存获益的临床试验数据，以及在辅助治疗中使用 BV 没有获益。还对常见的 BV 毒性和可能的 BV 耐药机制进行了讨论。
尽管 BV 在 mCRC 中显示出疗效，但迫切需要提高对其作用机制和 BV 耐药性的认识。此外，还需要确定预测 BV 疗效和毒性的生物标志物。
