CRUK Cambridge Institute, University of Cambridge, Cambridge, UK.
Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute, Jeffrey Cheah Biomedical Centre, University of Cambridge, Cambridge, UK.
Nat Rev Cancer. 2023 Oct;23(10):710-724. doi: 10.1038/s41568-023-00602-5. Epub 2023 Jul 24.
Cancer has been a leading cause of death for decades. This dismal statistic has increased efforts to prevent the disease or to detect it early, when treatment is less invasive, relatively inexpensive and more likely to cure. But precisely how tissues are transformed continues to provoke controversy and debate, hindering cancer prevention and early intervention strategies. Various theories of cancer origins have emerged, including the suggestion that it is 'bad luck': the inevitable consequence of random mutations in proliferating stem cells. In this Review, we discuss the principal theories of cancer origins and the relative importance of the factors that underpin them. The body of available evidence suggests that developing and ageing tissues 'walk a tightrope', retaining adequate levels of cell plasticity to generate and maintain tissues while avoiding overstepping into transformation. Rather than viewing cancer as 'bad luck', understanding the complex choreography of cell intrinsic and extrinsic factors that characterize transformation holds promise to discover effective new ways to prevent, detect and stop cancer before it becomes incurable.
几十年来，癌症一直是主要的死亡原因。这一悲惨的统计数据增加了人们预防癌症或早期发现癌症的努力，因为在这个阶段，治疗的侵入性更小、相对便宜，并且更有可能治愈。但是，组织究竟是如何发生转变的，仍然存在争议，这阻碍了癌症预防和早期干预策略的制定。癌症起源的各种理论已经出现，包括癌症是“运气不好”的观点：这是增殖干细胞中随机突变的必然结果。在这篇综述中，我们讨论了癌症起源的主要理论以及支撑这些理论的因素的相对重要性。现有的大量证据表明，发育和衰老的组织“如履薄冰”，保持足够水平的细胞可塑性，以产生和维持组织，同时避免过度转变为肿瘤。与其将癌症视为“运气不好”，不如理解细胞内在和外在因素的复杂编舞，这些因素决定了肿瘤的转化，这有望为预防、检测和阻止癌症在不可治愈之前提供有效的新方法。
