Gatenby Robert A, Gillies Robert J
Department of Radiology, University of Arizona, 1501 N Campbell Avenue, Tucson, Arizona 85724, USA.
Nat Rev Cancer. 2008 Jan;8(1):56-61. doi: 10.1038/nrc2255.
We propose that carcinogenesis requires tumour populations to surmount six distinct microenvironmental proliferation barriers that arise in the adaptive landscapes of normal and premalignant populations growing from epithelial surfaces. Somatic evolution of invasive cancer can then be viewed as a sequence of phenotypical adaptations to these barriers. The genotypical and phenotypical heterogeneity of cancer populations is explained by an equivalence principle in which multiple strategies can successfully adapt to the same barrier. This model provides a theoretical framework in which the diverse cancer genotypes and phenotypes can be understood according to their roles as adaptive strategies to overcome specific microenvironmental growth constraints.
我们提出，癌症发生需要肿瘤群体跨越六个不同的微环境增殖障碍，这些障碍出现在从上皮表面生长的正常和癌前群体的适应性景观中。侵袭性癌症的体细胞进化随后可被视为对这些障碍的一系列表型适应。癌症群体的基因型和表型异质性可以用一个等效原理来解释，即多种策略可以成功适应同一障碍。该模型提供了一个理论框架，在这个框架中，可以根据其作为克服特定微环境生长限制的适应性策略的作用来理解不同的癌症基因型和表型。
