Harry Jordan A, Ormiston Mark L
Department of Medicine, Queen's University, Kingston, ON, Canada.
Department of Biomedical and Molecular Sciences, Queen's University, Kingston, ON, Canada.
Front Oncol. 2021 Dec 3;11:772305. doi: 10.3389/fonc.2021.772305. eCollection 2021.
Breast cancer is the most common cancer affecting women and is the second leading cause of cancer related death worldwide. Angiogenesis, the process of new blood vessel development from pre-existing vasculature, has been implicated in the growth, progression, and metastasis of cancer. Tumor angiogenesis has been explored as a key therapeutic target for decades, as the blockade of this process holds the potential to reduce the oxygen and nutrient supplies that are required for tumor growth. However, many existing anti-angiogenic approaches, such as those targeting Vascular Endothelial Growth Factor, Notch, and Angiopoietin signaling, have been associated with severe side-effects, limited survival advantage, and enhanced cancer regrowth rates. To address these setbacks, alternative pathways involved in the regulation of tumor angiogenesis are being explored, including those involving Bone Morphogenetic Protein-9 signaling, the Sonic Hedgehog pathway, Cyclooxygenase-2, p38-mitogen-activated protein kinase, and Chemokine Ligand 18. This review article will introduce the concept of tumor angiogenesis in the context of breast cancer, followed by an overview of current anti-angiogenic therapies, associated resistance mechanisms and novel therapeutic targets.
乳腺癌是影响女性的最常见癌症，也是全球癌症相关死亡的第二大主要原因。血管生成是指从预先存在的脉管系统发育出新血管的过程，它与癌症的生长、进展和转移有关。几十年来，肿瘤血管生成一直被作为一个关键的治疗靶点进行探索，因为阻断这一过程有可能减少肿瘤生长所需的氧气和营养供应。然而，许多现有的抗血管生成方法，如那些针对血管内皮生长因子、Notch和血管生成素信号传导的方法，都与严重的副作用、有限的生存优势以及更高的癌症复发率相关。为了解决这些挫折，人们正在探索参与调节肿瘤血管生成的替代途径，包括那些涉及骨形态发生蛋白-9信号传导、音猬因子途径、环氧化酶-2、p38丝裂原活化蛋白激酶和趋化因子配体18的途径。这篇综述文章将在乳腺癌的背景下介绍肿瘤血管生成的概念，随后概述当前的抗血管生成疗法、相关的耐药机制和新的治疗靶点。
