a Medical Oncology Unit 1, Clinical and Experimental Oncology Department , Veneto Institute of Oncology IOV-IRCCS , Padua , Italy.
b Division of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine , University of Southern California , Los Angeles , CA , USA.
Expert Rev Anticancer Ther. 2018 Mar;18(3):251-266. doi: 10.1080/14737140.2018.1428092. Epub 2018 Jan 19.
Angiogenesis is a complex process regulated by several pro- and anti-angiogenic factors, thus the loss of its fine equilibrium plays a key role in colorectal cancer (CRC) development and progression. Therapeutic agents targeting VEGF/VEGFR signaling, the main regulator of this process, proved to be effective across different treatment lines in metastatic CRC (mCRC) and contributed greatly to improve patients' survival in recent years. Areas covered: This review aimed to summarize the actual body of knowledge available on the VEGF pathway in CRC, including currently available anti-angiogenic drugs and treatment challenges, mechanisms of resistance, promising predictive biomarkers and future perspectives. Expert commentary: Angiogenesis inhibition in subsequent lines of treatment is a valid strategy in the continuum of care of mCRC patients. In this scenario, the availability of multiple agents warrants to tailor therapy to an individualized approach. However, the validation of predictive biomarkers to aid therapeutic decisions remains an issue. Intrinsic and adaptive resistance to anti-angiogenic agents comprises distinct and intertwined processes, eventually leading to treatment failure and disease progression. The expanding knowledge on the mechanisms underlying the angiogenesis pathway, different potential treatment targets and mechanisms of tumor resistance, may lead to promising new perspectives in this field.
血管生成是一个由多种促血管生成和抗血管生成因子调节的复杂过程，因此其精细平衡的丧失在结直肠癌（CRC）的发展和进展中起着关键作用。针对血管内皮生长因子/血管内皮生长因子受体（VEGF/VEGFR）信号通路的治疗药物是这一过程的主要调节剂，已被证明在转移性 CRC（mCRC）的不同治疗线中有效，并在近年来大大提高了患者的生存率。
本综述旨在总结 CRC 中 VEGF 通路的现有知识体系，包括目前可用的抗血管生成药物和治疗挑战、耐药机制、有前途的预测生物标志物以及未来展望。
在 mCRC 患者的连续护理中，后续治疗线中的血管生成抑制是一种有效的策略。在这种情况下，多种药物的应用使得能够针对个体化方法进行治疗。然而，预测生物标志物的验证以辅助治疗决策仍然是一个问题。抗血管生成药物的内在和获得性耐药包括不同且相互交织的过程，最终导致治疗失败和疾病进展。对血管生成途径、不同潜在治疗靶点和肿瘤耐药机制的机制的不断深入了解，可能会为该领域带来有希望的新视角。
