Balk Bradley, Goodrich David W
Department of Pharmacology and Therapeutics, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA.
Department of Urology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA.
Cancer Heterog Plast. 2024;1(2). doi: 10.47248/chp2401020010. Epub 2024 Dec 13.
Phenotypic plasticity, the capacity of cells to transition between distinct phenotypic and lineage states over time, is a genetically and epigenetically encoded trait essential for normal development and adult tissue homeostasis. In cancer, phenotypic plasticity programs can be deployed aberrantly to enable disease progression and acquired therapeutic resistance. Cancer phenotypic plasticity is a current barrier to achieving cures for advanced cancers using available molecularly targeted therapies. This review summarizes the complex and interconnected molecular pathways implicated in phenotypic plasticity, both in the context of normal tissue homeostasis and cancer. Molecular pathways convergent between these contexts are highlighted while pathways enabling plasticity are distinguished from those that specify the phenotype of already plastic cells. Key unresolved questions in the field are discussed along with emerging technologies that may be used to help answer them.
表型可塑性是指细胞随时间在不同表型和谱系状态之间转变的能力，是一种由基因和表观遗传编码的性状，对正常发育和成年组织稳态至关重要。在癌症中，表型可塑性程序可能会异常启动，以促进疾病进展和产生获得性治疗耐药性。癌症表型可塑性是目前使用现有分子靶向疗法治愈晚期癌症的一个障碍。本综述总结了在正常组织稳态和癌症背景下与表型可塑性相关的复杂且相互关联的分子途径。重点介绍了这些背景之间趋同的分子途径，同时区分了促成可塑性的途径与那些决定已具有可塑性细胞表型的途径。文中还讨论了该领域尚未解决的关键问题以及可能用于帮助解答这些问题的新兴技术。
