Institute for Biocomplexity and Informatics, University of Calgary, Alberta, Canada.
Semin Cancer Biol. 2011 Jun;21(3):183-99. doi: 10.1016/j.semcancer.2011.05.003. Epub 2011 May 26.
The cracks in the paradigm of oncogenic mutations and somatic evolution as driving force of tumorigenesis, lucidly exposed by the dynamic heterogeneity of "cancer stem cells" or the diffuse results of cancer genome sequencing projects, indicate the need for a more encompassing theory of cancer that reaches beyond the current proximate explanations based on individual genetic pathways. One such integrative concept, derived from first principles of the dynamics of gene regulatory networks, is that cancerous cell states are attractor states, just like normal cell types are. Here we extend the concept of cancer attractors to illuminate a more profound property of cancer initiation: its inherent inevitability in the light of metazoan evolution. Using Waddington's Epigenetic Landscape as a conceptual aid, for which we present a mathematical and evolutionary foundation, we propose that cancer is intrinsically linked to ontogenesis and phylogenesis. This explanatory rather than enumerating review uses a formal argumentation structure that is atypical in modern experimental biology but may hopefully offer a new coherent perspective to reconcile many conflicts between new findings and the old thinking in the categories of linear oncogenic pathways.
致癌基因突变和体细胞进化作为肿瘤发生驱动力的范式出现了裂痕，“癌症干细胞”的动态异质性或癌症基因组测序项目的广泛结果清晰地揭示了这一点，这表明需要一种更全面的癌症理论，超越基于个体遗传途径的当前近似解释。这样一个综合概念，源自基因调控网络动力学的基本原理，是癌细胞状态是吸引子状态，就像正常细胞类型一样。在这里，我们将癌症吸引子的概念扩展到阐明癌症起始的一个更深层次的特性：根据后生动物进化，其内在的必然性。我们使用 Waddington 的表观遗传景观作为概念辅助，为此我们提出了一个数学和进化基础，我们提出癌症与个体发生和系统发生内在相关。这个解释性的而不是列举性的综述使用了一种形式论证结构，这在现代实验生物学中并不典型，但希望能提供一个新的连贯视角，以调和新发现和线性致癌途径类别中旧思维之间的许多冲突。
