Oncologist：贝伐单抗联合化疗可能提高疗效

针对肿瘤新生血管形成或血管生成的治疗手段在癌症治疗中占有重要地位，贝伐单抗等针对血管内皮生长因子（VEGF）的单克隆抗体生物制剂在临床上已被广泛运用。

抗血管生成疗法的基本原理是如果肿瘤获得新的血液供应能力有限，那么它们的生长和转移能力也会受到限制。更多的证据表明，修饰和/或“正常化”不规则的肿瘤血管，减少缺氧可加强肿瘤细胞毒性化疗（CT）的功效。

事实上，对于转移性大肠直肠癌，贝伐单抗联合CT方案的疗效优于单独CT疗法。虽然接受联合疗法的患者在开始约2个月时间内治疗结果无进展，但患者整体生存时间比单独接受CT的患者要好，其原因可能是因为血管替代生成途径或低氧应激驱动肿瘤产生耐受。

除了VEGF，其它血管内皮生长因子家族成员作为一个复杂血管生成调控网络的一部分，也有助于调节肿瘤血管生成，也可能有助于肿瘤产生耐药抵抗。因此将这些概念融入到新的抗血管生成疗法可能有助于克服肿瘤的耐药机制，治疗周期可能会更长和功效可能更大。

Overcoming Resistance to Antiangiogenic Therapies

Sabine Tejpara, Hans Prenena and Massimiliano Mazzoneb,c

The concept of targeting new blood vessel formation, or angiogenesis, in tumors is an important advancement in cancer therapy, resulting, in part, from the development of such biologic agents as bevacizumab, a monoclonal antibody directed against vascular endothelial growth factor (VEGF)-A. The rationale for antiangiogenic therapy is based on the hypothesis that if tumors are limited in their capacity to obtain a new blood supply, so too is their capacity for growth and metastasis. Additional evidence suggests that pruning and/or “normalization” of irregular tumor vasculature and reduction of hypoxia may facilitate greater access of cytotoxic chemotherapy (CT) to the tumor. Indeed, for metastatic colorectal cancer, bevacizumab in combination with established CT regimens has efficacy superior to that of CT alone. Despite ∼2-month longer progression-free and overall survival times than with CT alone, patients still progress, possibly because of alternative angiogenic “escape” pathways that emerge independent of VEGF-A, or are driven by hypoxic stress on the tumor. Other VEGF family members may contribute to resistance, and many factors that contribute to the regulation of tumor angiogenesis function as part of a complex network, existing in different concentrations and spatiotemporal gradients and producing a wide range of biologic responses. Integrating these concepts into the design and evaluation of new antiangiogenic therapies may help overcome resistance mechanisms and allow for greater efficacy over longer treatment periods.

原始链接：

Sabine Tejpara, Hans Prenena and Massimiliano Mazzoneb,c. Overcoming Resistance to Antiangiogenic Therapies. Doi:10.1634/theoncologist.2012-0068.