肿瘤内异质性在癌症进化中的生物学和治疗影响。

Biological and therapeutic impact of intratumor heterogeneity in cancer evolution.

机构信息

Cancer Research UK London Research Institute, London WC2A 3LY, UK; Centre for Mathematics & Physics in the Life Science & Experimental Biology (CoMPLEX), University College London, London WC1E 6BT, UK.

Cancer Research UK London Research Institute, London WC2A 3LY, UK; UCL Cancer Institute, Paul O'Gorman Building, Huntley Street, London WC1E 6DD, UK.

出版信息

Cancer Cell. 2015 Jan 12;27(1):15-26. doi: 10.1016/j.ccell.2014.12.001.

DOI:10.1016/j.ccell.2014.12.001

PMID:25584892

Abstract

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.

摘要

精准医学需要对癌症基因和突变过程有深入了解，还需要认识到在肿瘤进化过程中这些基因和突变在癌细胞中是如何异质性存在的。在这里，我们探讨了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，并探讨了它们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约束和偶然性的证据，并强调了肿瘤内多样性的临床意义。我们概述了基于基因组的靶向治疗的局限性，并探讨了未来的策略，包括免疫和适应性方法，以应对这一治疗挑战。