Cancer is driven by genomic mutations in ‘cancer driver’ genes, which have essential roles in tumor development. These mutations may be caused by exposure to mutagens in the environment or by endogenous DNA-replication errors in tissue stem cells. Recent observations of abundant mutations, including cancer driver mutations, in histologically normal human tissues suggest that mutations alone are not sufficient for tumor development, thus prompting the question of how single mutant cells give rise to neoplasia. In a concept supported by decades-old data from mouse tumor models, non-mutagenic tumor-promoting agents have been posited to activate the proliferation of dormant mutated cells, thus generating actively growing lesions, with the promotion stage as the rate-limiting step in tumor formation. Non-mutagenic promoting agents, either endogenous or environmental, may therefore have a more important role in human cancer etiology than previously thought.

癌症是由“癌症驱动”基因的基因组突变驱动的，这些基因在肿瘤发展中起着至关重要的作用。这些突变可能是由于暴露于环境中的诱变剂或组织干细胞中的内源性 DNA 复制错误引起的。最近对组织学正常人体组织中大量突变（包括癌症驱动突变）的观察表明，仅突变不足以促进肿瘤的发展，因此提出了单个突变细胞如何导致肿瘤形成的问题。在一个由小鼠肿瘤模型的数十年数据支持的概念中，非诱变促肿瘤剂被认为可以激活休眠突变细胞的增殖，从而产生活跃生长的病变，促进阶段是肿瘤形成。非诱变促进剂，