Resistance to anticancer therapy still represents one of the main obstacles to cancer treatment. Numerous components of the tumor microenvironment (TME) contribute significantly to the acquisition of drug resistance. Microenvironmental pressures arising during cancer evolution foster tumor heterogeneity and facilitate the emergence of drug-resistant clones. In particular, metabolic pressures arising in the TME may favor epigenetic adaptations supporting the acquisition of persistence features in tumor cells. Tumor-persistent cells (TPCs) are characterized by high phenotypic and metabolic plasticity, representing a noticeable advantage in chemo- and radio-resistance. Understanding the crosslink between the evolution of metabolic pressures in the TME, epigenetics, and TPC evolution is significant for developing novel therapeutic strategies specifically targeting TPC vulnerabilities to overcome drug resistance.

中文翻译：

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代谢挑战者选择肿瘤持续性细胞

对抗癌治疗的抵抗仍然是癌症治疗的主要障碍之一。肿瘤微环境（TME）的许多成分对耐药性的获得有显着影响。癌症进化过程中产生的微环境压力促进了肿瘤异质性并促进了耐药克隆的出现。特别是，TME 中产生的代谢压力可能有利于支持肿瘤细胞持久性特征获得的表观遗传适应。肿瘤持续细胞（TPC）具有高表型和代谢可塑性的特点，在化疗和放射抗性方面具有显着的优势。了解 TME 中代谢压力的进化、表观遗传学和 TPC 进化之间的交联对于开发专门针对 TPC 脆弱性以克服耐药性的新治疗策略具有重要意义。