The atavistic theory of cancer posits that cancer emerges and progresses through the reversion of cellular phenotypes to more ancestral types with genomic and epigenetic changes deactivating recently evolved genetic modules and activating ancient survival mechanisms. This theory aims at explaining the known cancer hallmarks and the paradox of cancer’s predictable progression despite the randomness of genetic mutations. Lineweaver and colleagues recently proposed the Serial Atavism Model (SAM), an enhanced version of the atavistic theory, which suggests that cancer progression involves multiple atavistic reversions where cells regress through evolutionary stages, losing recently evolved traits first and reactivating primitive ones later. The Warburg effect, where cancer cells upregulate glycolysis and lactate production in the presence of oxygen instead of using oxidative phosphorylation, is one of the key feature of the SAM. It is associated with the metabolism of ancient cells living on Earth before the oxygenation of the atmosphere. This review addresses the question of whether cancer metabolism can be considered as an atavistic reversion. By analyzing several known characteristics of cancer metabolism, we reach the conclusion that this version of the atavistic theory does not provide an adequate conceptual frame for cancer research. Cancer metabolism spans a whole spectrum of metabolic states which cannot be fully explained by a sequential reversion to an ancient state. Moreover, we interrogate the nature of cancer metabolism and discuss its characteristics within the framework of the SAM.
癌症的返祖理论认为，癌症的发生和发展是通过细胞表型向更原始类型的逆转而实现的，其基因组和表观遗传变化使近期进化的遗传模块失活，并激活古老的生存机制。该理论旨在解释已知的癌症特征，以及尽管基因突变具有随机性，但癌症进展却可预测的矛盾现象。Lineweaver及其同事最近提出了连续返祖模型（SAM），这是返祖理论的增强版本，该模型认为癌症进展涉及多次返祖逆转，细胞通过进化阶段逐步退化，先失去近期进化的特征，随后重新激活原始特征。瓦博格效应（即癌细胞在有氧条件下上调糖酵解和乳酸生成，而非使用氧化磷酸化）是SAM的关键特征之一。这与地球大气氧化之前存在的古老细胞的代谢方式相关。本综述探讨了癌症代谢是否可被视为一种返祖逆转的问题。通过分析癌症代谢的若干已知特征，我们得出结论：这一版本的返祖理论并未为癌症研究提供充分的概念框架。癌症代谢涵盖了一系列代谢状态，无法完全通过向古老状态的顺序逆转来解释。此外，我们探讨了癌症代谢的本质，并在SAM框架内讨论了其特征。
肿瘤(癌症)患者之家