Tissot Tazzio, Ujvari Beata, Solary Eric, Lassus Patrice, Roche Benjamin, Thomas Frédéric
CREEC/MIVEGEC, UMR IRD/CNRS/UM 5290, 911 Avenue Agropolis, BP 64501, 34394 Montpellier Cedex 5, France.
Centre for Integrative Ecology, School of Life and Environmental Sciences, Deakin University, Waurn Ponds, Australia.
Biochim Biophys Acta. 2016 Apr;1865(2):147-54. doi: 10.1016/j.bbcan.2016.01.005. Epub 2016 Feb 2.
By definition, a driver mutation confers a growth advantage to the cancer cell in which it occurs, while a passenger mutation does not: the former is usually considered as the engine of cancer progression, while the latter is not. Actually, the effects of a given mutation depend on the genetic background of the cell in which it appears, thus can differ in the subclones that form a tumor. In addition to cell-autonomous effects generated by the mutations, non-cell-autonomous effects shape the phenotype of a cancer cell. Here, we review the evidence that a network of biological interactions between subclones drives cancer cell adaptation and amplifies intra-tumor heterogeneity. Integrating the role of mutations in tumor ecosystems generates innovative strategies targeting the tumor ecosystem's weaknesses to improve cancer treatment.
根据定义，驱动突变赋予发生该突变的癌细胞生长优势，而乘客突变则不然：前者通常被视为癌症进展的引擎，而后者则不是。实际上，特定突变的影响取决于其出现的细胞的遗传背景，因此在形成肿瘤的亚克隆中可能有所不同。除了突变产生的细胞自主效应外，非细胞自主效应也塑造了癌细胞的表型。在这里，我们综述了亚克隆之间的生物相互作用网络驱动癌细胞适应并放大肿瘤内异质性的证据。整合突变在肿瘤生态系统中的作用可产生针对肿瘤生态系统弱点的创新策略，以改善癌症治疗。
