Department of Medicine, Vanderbilt University School of Medicine, A-4323 MCN, 1161 21st Avenue South, Nashville, TN 37232-2363, USA.
Semin Cell Dev Biol. 2012 Feb;23(1):102-8. doi: 10.1016/j.semcdb.2011.10.014. Epub 2011 Oct 21.
Pre-clinical studies provide compelling evidence that members of the Eph family of receptor tyrosine kinases and their ephrin ligands promote tumor growth, invasion and metastasis, and neovascularization. Tumor suppressive roles have also been reported for the receptors, and ligand-dependent versus ligand-independent signaling has emerged as one key mechanism underlying tumor suppressive function as opposed to oncogenic effects. Determining how these observations relate to clinical outcome is a crucial step for translating the biological and mechanistic data into new molecularly targeted therapies. Expression profiling in human patient samples bridges this gap and provides valuable clinical relevance to laboratory observations. In addition to analyses performed using privately assembled patient tumor samples, publically available microarray datasets and tissue microarrays linked to clinical data have emerged as tractable tools for addressing the clinical relevance of specific molecules and families of related molecules. This review summarizes the clinical relevance of specific Eph and ephrin molecules in human breast, colorectal, and lung cancers.
临床前研究提供了令人信服的证据,表明 Eph 受体酪氨酸激酶家族成员及其配体 ephrins 促进肿瘤生长、侵袭和转移以及新血管生成。受体也具有肿瘤抑制作用,配体依赖性与配体非依赖性信号转导已成为肿瘤抑制功能而非致癌作用的关键机制之一。确定这些观察结果与临床结果的关系是将生物学和机制数据转化为新的分子靶向治疗的关键步骤。在人类患者样本中的表达谱分析填补了这一空白,并为实验室观察提供了有价值的临床相关性。除了使用私人收集的患者肿瘤样本进行的分析外,公共可用的微阵列数据集和与临床数据相关的组织微阵列已成为解决特定分子及其相关分子家族的临床相关性的可行工具。这篇综述总结了 Eph 和 ephrin 分子在人类乳腺癌、结直肠癌和肺癌中的临床相关性。