Department of Pharmacology and Toxicology, University of Utah, Salt Lake City, UT, USA.
Department of Oncological Sciences, University of Utah, Salt Lake City, UT, USA.
J Mol Med (Berl). 2017 Nov;95(11):1167-1178. doi: 10.1007/s00109-017-1587-4. Epub 2017 Sep 4.
Tumor heterogeneity has been identified at various -omic levels. The tumor genome, transcriptome, proteome, and phenome can vary widely across cells in patient tumors and are influenced by tumor cell interactions with heterogeneous physical conditions and cellular components of the tumor microenvironment. Here, we explore the concept that while variation exists at multiple -omic levels, changes at each of these levels converge on the same pathways and lead to convergent phenotypes in tumors that can provide common drug targets. These phenotypes include cellular growth and proliferation, sustained oncogenic signaling, and immune avoidance, among others. Tumor heterogeneity complicates treatment of patient cancers as it leads to varied response to therapies. Identification of convergent cellular phenotypes arising in patient cancers and targeted therapies that reverse them has the potential to transform the way clinicians treat these cancers and to improve patient outcome.
肿瘤异质性在各种“组学”水平上都有体现。肿瘤的基因组、转录组、蛋白质组和表型组在患者肿瘤的细胞之间存在广泛差异，并且受到肿瘤细胞与肿瘤微环境中异质物理条件和细胞成分相互作用的影响。在这里，我们探讨了这样一种概念，即在多个“组学”水平上存在差异的同时，这些水平上的变化集中在相同的途径上，并导致肿瘤中具有趋同表型的出现，这些表型可为肿瘤提供共同的药物靶点。这些表型包括细胞生长和增殖、持续的致癌信号以及免疫逃避等。肿瘤异质性使患者癌症的治疗变得复杂，因为它导致对治疗的反应各不相同。识别出在患者癌症中出现的趋同细胞表型，并针对这些表型进行治疗，有可能改变临床医生治疗这些癌症的方式，并改善患者的预后。
