Biological and Therapeutic Impact of Intratumor Heterogeneity in Cancer Evolution
Biological and Therapeutic Impact of Intratumor Heterogeneity in Cancer Evolution
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DOI：
10.1016/j.ccell.2014.12.001
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发表时间：
2015-01-12
期刊：
影响因子：
50.3
通讯作者：
Swanton, Charles
中科院分区：
文献类型：
--
作者：
McGranahan, Nicholas;Swanton, Charles
精准医学需要了解癌症基因和突变过程，以及了解肿瘤进化过程中癌细胞中这些基因和突变过程的异质性程度。在这里，我们探索塑造癌症基因组的过程，将这些过程置于肿瘤进化的背景下及其对肿瘤内异质性和药物开发的影响。我们回顾了肿瘤进化的限制和意外事件的证据，并强调了肿瘤内多样性的临床意义。我们概述了基因组驱动的靶向治疗的局限性，并探索未来的策略，包括免疫和适应性方法，以应对这一治疗挑战。
Precision medicine requires an understanding of cancer genes and mutational processes, as well as an appreciation of the extent to which these are found heterogeneously in cancer cells during tumor evolution. Here, we explore the processes shaping the cancer genome, placing these within the context of tumor evolution and their impact on intratumor heterogeneity and drug development. We review evidence for constraints and contingencies to tumor evolution and highlight the clinical implications of diversity within tumors. We outline the limitations of genome-driven targeted therapies and explore future strategies, including immune and adaptive approaches, to address this therapeutic challenge.