加拿大多伦多大学Catherine A. O’Brien等研究人员合作发现，结直肠癌细胞能够进入滞育样状态来逃避化疗。相关论文于2021年1月7日发表在《细胞》杂志上。
研究人员在患者来源的结肠直肠癌模型中结合了细胞条形码和数学模型，从而鉴定和表征了化疗反应中的药物耐受性持久性（DTP）。条形码分析显示，进入DTP状态并在停止治疗后复发肿瘤的克隆复杂性没有丢失。这些数据符合数学模型，即所有癌细胞（而不是小亚群）都具有成为DTP的等效能力。
从机制上讲，研究人员确定了DTP与滞育具有显著的转录和功能相似性；滞育是由不利环境条件引发的悬浮胚胎发育可逆状态。
这项研究提供了关于癌细胞如何使用发育上保守的机制来驱动DTP状态的见解，并指出了靶向DTP的治疗潜力。
据介绍，癌细胞能够进入可逆的DTP状态来逃避化疗和靶向药物引起的死亡。人们日益认识到，DTP是治疗失败和肿瘤复发的重要驱动力。
附：英文原文
Title: Colorectal Cancer Cells Enter a Diapause-like DTP State to Survive Chemotherapy
Author: Sumaiyah K. Rehman, Jennifer Haynes, Evelyne Collignon, Kevin R. Brown, Yadong Wang, Allison M.L. Nixon, Jeffrey P. Bruce, Jeffrey A. Wintersinger, Arvind Singh Mer, Edwyn B.L. Lo, Cherry Leung, Evelyne Lima-Fernandes, Nicholas M. Pedley, Fraser Soares, Sophie McGibbon, Housheng Hansen He, Aaron Pollet, Trevor J. Pugh, Benjamin Haibe-Kains, Quaid Morris, Miguel Ramalho-Santos, Sidhartha Goyal, Jason Moffat, Catherine A. O’Brien
Issue&Volume: 2021/01/07
Abstract: Cancer cells enter a reversible drug-tolerant persister (DTP) state to evade deathfrom chemotherapy and targeted agents. It is increasingly appreciated that DTPs areimportant drivers of therapy failure and tumor relapse. We combined cellular barcodingand mathematical modeling in patient-derived colorectal cancer models to identifyand characterize DTPs in response to chemotherapy. Barcode analysis revealed no lossof clonal complexity of tumors that entered the DTP state and recurred following treatmentcessation. Our data fit a mathematical model where all cancer cells, and not a smallsubpopulation, possess an equipotent capacity to become DTPs. Mechanistically, wedetermined that DTPs display remarkable transcriptional and functional similaritiesto diapause, a reversible state of suspended embryonic development triggered by unfavorableenvironmental conditions. Our study provides insight into how cancer cells use a developmentallyconserved mechanism to drive the DTP state, pointing to novel therapeutic opportunitiesto target DTPs.
DOI: 10.1016/j.cell.2020.11.018
Source: https://www.cell.com/cell/fulltext/S0092-8674(20)31535-X