Department of Hematology, Instituto Portugues de Oncologia de Lisboa Francisco Gentil, Lisboa, Portugal.
School of Medicine, University of Southampton, Southampton, UK.
Leukemia. 2020 Sep;34(9):2279-2284. doi: 10.1038/s41375-020-0957-z. Epub 2020 Jul 6.
Our concept of cancer latency, the interval from when a cancer starts until it is diagnosed, has changed dramatically. A prior widely-used definition was the interval between an exposure to a cancer-causing substance and cancer diagnosis. However, this definition does not accurately reflect current knowledge of how most cancers develop assuming, mostly incorrectly, one exposure is the sole cause of a cancer, ignoring the possibility the cancer being considered would have developed anyway but that the exposure accelerated cancer development and eliding the randomness in when a cancer is diagnosed. We show, using chronic myeloid leukaemia as a model, that defining cancer latency is not as simple as it once seemed. It is difficult or impossible to know at which event or mutation to start to clock to measure cancer latency. It is equally difficult to know when to stop the clock given the stochastic nature of when cancers are diagnosed. Importantly, even in genetically-identical twins with the same driver mutation intervals to develop cancer vary substantially. And we discuss other confonders. Clearly we need a new definition of cancer latency or we need to abandon the concept of cancer latency in the modern era of cancer biology.
我们对癌症潜伏期的概念，即从癌症开始到被诊断出来的时间间隔，已经发生了巨大的变化。以前广泛使用的定义是癌症起因物质暴露和癌症诊断之间的时间间隔。然而，这个定义并不能准确反映目前大多数癌症发展的知识，因为它假设大多数情况下，一次暴露是癌症的唯一原因，忽略了癌症本来就有可能发展的可能性，只是暴露加速了癌症的发展，并掩盖了癌症被诊断出来的随机性。我们以慢性髓性白血病为例，表明定义癌症潜伏期并不像以前看起来那么简单。要确定开始计时以测量癌症潜伏期的事件或突变，是很困难或不可能的。由于癌症诊断的随机性，要知道何时停止计时也同样困难。重要的是，即使是具有相同驱动突变的同卵双胞胎，发展癌症的时间间隔也有很大差异。我们还讨论了其他混杂因素。显然，我们需要一个新的癌症潜伏期定义，或者我们需要在癌症生物学的现代时代放弃癌症潜伏期的概念。
