Cancer hijacks embryonic development and adult wound repair mechanisms to fuel malignancy. Cancer frequently originates from de-regulated adult stem cells or progenitors, which are otherwise essential units for postnatal tissue remodeling and repair. Cancer genomics studies have revealed convergence of multiple cancers across organ sites, including squamous cell carcinomas (SCCs), a common group of cancers arising from the head and neck, esophagus, lung, cervix and skin. In this review, we summarize our current knowledge on the molecular drivers of SCCs, including these five major organ sites. We especially focus our discussion on lineage dependent driver genes and pathways, in the context of squamous development and stratification. We then use skin as a model to discuss the notion of field cancerization during SCC carcinogenesis, and cancer as a wound that never heals. Finally, we turn to the idea of context dependency widely observed in cancer driver genes, and outline literature support and possible explanations for their lineage specific functions. Through these discussions, we aim to provide an up-to-date summary of molecular mechanisms driving tumor plasticity in squamous cancers. Such basic knowledge will be helpful to inform the clinics for better stratifying cancer patients, revealing novel drug targets and providing effective treatment options.

中文翻译：

---

揭示鳞状细胞癌中的癌症谱系驱动因素。

癌症劫持胚胎发育和成人伤口修复机制以助长恶性肿瘤。癌症通常起源于失控的成体干细胞或祖细胞，它们是出生后组织重塑和修复的重要单位。癌症基因组学研究揭示了多种癌症在不同器官部位的融合，包括鳞状细胞癌（SCC），这是一组常见的源自头颈、食道、肺癌、子宫颈和皮肤的癌症。在这篇综述中，我们总结了目前对鳞状细胞癌分子驱动因素的了解，包括这五个主要器官部位。在鳞状细胞发育和分层的背景下，我们特别关注谱系依赖性驱动基因和途径的讨论。然后，我们使用皮肤作为模型来讨论鳞状细胞癌致癌过程中现场癌化的概念，以及癌症作为永不愈合的伤口的概念。最后，我们转向在癌症驱动基因中广泛观察到的背景依赖性的想法，并概述了其谱系特定功能的文献支持和可能的解释。通过这些讨论，我们的目标是提供驱动鳞状癌肿瘤可塑性的分子机制的最新总结。这些基础知识将有助于临床更好地对癌症患者进行分层，揭示新的药物靶点并提供有效的治疗方案。