论文标题

癌症缺失的标志:分化失调

A Missing Hallmark of Cancer: Dysregulation of Differentiation

论文作者

Compton, Zachary, Hanlon, Kathleen, Compton, Carolyn C., Aktipis, Athena, Maley, Carlo C.

论文摘要

癌细胞具有几乎普遍的特征,称为癌症的标志,包括复制永生和抵抗细胞死亡。几乎所有癌症中都存在失调的分化,但尚未被描述为癌症标志。像其他标志一样,失调的分化涉及通常使多细胞可能成为可能的细胞合作的分解 - 在这种情况下,会破坏人体细胞之间的劳动分裂。在描述了癌症的原始标志时,尚不清楚分化失调在机械上与生长抑制作用不同,但是现在这是已知的,这是考虑分化失调的进一步原因。失调的分化也具有临床实用性,因为它构成了病理分级的基础,可以预测临床结果,并且是旨在诱导分化的疗法的可行靶标。在这里,我们认为癌症的标志应接近通用,机械上的不同,并具有预后和/或治疗的临床实用性。失调的分化符合所有这些标准。

Cancer cells possess a nearly universal set of characteristics termed the hallmarks of cancer, including replicative immortality and resisting cell death. Dysregulated differentiation is present in virtually all cancers yet has not yet been described as a cancer hallmark. Like other hallmarks, dysregulated differentiation involves a breakdown of the cellular cooperation that typically makes multicellularity possible - in this case disrupting the division of labor among the cells of a body. At the time that the original hallmarks of cancer were described, it was not known that dysregulated differentiation was mechanistically distinct from growth inhibition, but now that this is known, it is a further reason to consider dysregulated differentiation a hallmark of cancer. Dysregulated differentiation also has clinical utility, as it forms the basis of pathological grading, predicts clinical outcomes, and is a viable target for therapies aimed at inducing differentiation. Here we argue that hallmarks of cancer should be near universal, mechanistically distinct, and have clinical utility for prognosis and/or therapy. Dysregulated differentiation meets all of these criteria.

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