Cancer Biology and Genetics Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Weill Cornell/Rockefeller/Sloan Kettering Tri-Institutional MD-PhD Program, New York, NY, 10065, USA.
Cancer Biology and Genetics Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Weill Cornell Graduate School of Medical Sciences, Cornell University, New York, NY, 10065, USA.
Trends Cancer. 2022 Sep;8(9):735-746. doi: 10.1016/j.trecan.2022.04.007. Epub 2022 May 23.
Cancer cells are plastic - they can assume a wide range of distinct phenotypes. Plasticity is integral to cancer initiation and progression, as well as to the emergence and maintenance of intratumoral heterogeneity. Furthermore, plastic cells can rapidly adapt to and evade therapy, which poses a challenge for effective cancer treatment. As such, targeting plasticity in cancer holds tremendous promise. Yet, the principles governing plasticity in cancer cells remain poorly understood. Here, we provide an overview of the fundamental molecular and cellular mechanisms that underlie plasticity in cancer and in other biological contexts, including development and regeneration. We propose a key role for high-plasticity cell states (HPCSs) as crucial nodes for cell state transitions and enablers of intra-tumoral heterogeneity.
癌细胞具有可塑性——它们可以呈现出多种不同的表型。可塑性是癌症发生和发展的基础,也是肿瘤内异质性出现和维持的基础。此外,具有可塑性的细胞可以迅速适应和逃避治疗,这给癌症的有效治疗带来了挑战。因此,针对癌症的可塑性具有巨大的潜力。然而,癌症细胞可塑性的控制原则仍知之甚少。在这里,我们概述了癌症和其他生物学背景(包括发育和再生)中可塑性的基本分子和细胞机制。我们提出了高可塑性细胞状态(HPCSs)作为细胞状态转变的关键节点和肿瘤内异质性的促进因素的重要作用。