針對腫瘤新生血管形成或血管生成的治療手段在癌癥治療中占有重要地位,，貝伐單抗等針對血管內(nèi)皮生長因子（VEGF）的單克隆抗體生物制劑在臨床上已被廣泛運用,。
抗血管生成療法的基本原理是如果腫瘤獲得新的血液供應(yīng)能力有限，那么它們的生長和轉(zhuǎn)移能力也會受到限制,。更多的證據(jù)表明,，修飾和/或“正常化”不規(guī)則的腫瘤血管,，減少缺氧可加強腫瘤細胞毒性化療（CT）的功效,。
事實上，對于轉(zhuǎn)移性大腸直腸癌,，貝伐單抗聯(lián)合CT方案的療效優(yōu)于單獨CT療法,。雖然接受聯(lián)合療法的患者在開始約2個月時間內(nèi)治療結(jié)果無進展，但患者整體生存時間比單獨接受CT的患者要好,，其原因可能是因為血管替代生成途徑或低氧應(yīng)激驅(qū)動腫瘤產(chǎn)生耐受,。
除了VEGF，其它血管內(nèi)皮生長因子家族成員作為一個復(fù)雜血管生成調(diào)控網(wǎng)絡(luò)的一部分,，也有助于調(diào)節(jié)腫瘤血管生成,，也可能有助于腫瘤產(chǎn)生耐藥抵抗。因此將這些概念融入到新的抗血管生成療法可能有助于克服腫瘤的耐藥機制,，治療周期可能會更長和功效可能更大,。（生物谷：Bioon.com）
doi:10.1634/theoncologist.2012-0068
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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.
