Cancer Research Center, Ege University, Izmir, Turkey.
Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.
Adv Exp Med Biol. 2021;1270:57-71. doi: 10.1007/978-3-030-47189-7_4.
Pioneering experiments performed by Harold Varmus and Mike Bishop in 1976 led to one of the most influential discoveries in cancer research and identified the first cancer-causing oncogene called Src. Later experimental and clinical evidence suggested that Src kinase plays a significant role in promoting tumor growth and progression and its activity is associated with poor patient survival. Thus, several Src inhibitors were developed and approved by FDA for treatment of cancer patients. Tumor microenvironment (TME) is a highly complex and dynamic milieu where significant cross-talk occurs between cancer cells and TME components, which consist of tumor-associated macrophages, fibroblasts, and other immune and vascular cells. Growth factors and chemokines activate multiple signaling cascades in TME and induce multiple kinases and pathways, including Src, leading to tumor growth, invasion/metastasis, angiogenesis, drug resistance, and progression. Here, we will systemically evaluate recent findings regarding regulation of Src and significance of targeting Src in cancer therapy.
哈罗德·瓦慕斯（Harold Varmus）和迈克·毕晓普（Mike Bishop）于 1976 年进行的开创性实验导致了癌症研究中最具影响力的发现之一，并确定了第一个致癌的癌基因，称为 Src。后来的实验和临床证据表明，Src 激酶在促进肿瘤生长和进展中发挥重要作用，其活性与患者预后不良相关。因此，几种 Src 抑制剂已被 FDA 开发并批准用于癌症患者的治疗。肿瘤微环境（TME）是一个高度复杂和动态的环境，其中癌细胞与 TME 成分之间发生着显著的串扰，这些成分包括肿瘤相关巨噬细胞、成纤维细胞以及其他免疫和血管细胞。生长因子和趋化因子在 TME 中激活多种信号级联反应，并诱导多种激酶和途径，包括 Src，从而导致肿瘤生长、侵袭/转移、血管生成、耐药性和进展。在这里，我们将系统地评估关于 Src 调节及其在癌症治疗中靶向 Src 的重要性的最新发现。
