癌症中应激颗粒驱动的耐药机制及新兴策略
Stress granules (SGs) are dynamic, membraneless organelles that form in response to stress and play pivotal roles in translational control, RNA metabolism, and cell survival. In cancer, SGs are increasingly recognized as central mediators of therapy resistance, enabling malignant cells to evade apoptosis, reprogram metabolism, and modulate immune responses. Understanding the mechanistic and clinical insights into SG kinetics in healthy versus cancer cells holds significant potential for targeting them in precision oncology. This review integrates current knowledge on how chemotherapeutic agents, oncogenic signaling pathways, and tumor microenvironmental stressors promote SG formation, as well as evidence of altered SG kinetics across tumor types. We further highlight how the upregulation of SG components within the tumor microenvironment shapes cancer cell behavior and adaptability, and how crosstalk between SGs and other biomolecular condensates could contribute to resistance. Finally, we discuss emerging therapeutic strategies targeting SGs, including kinase inhibitors and modulators of SG dynamics, and propose that SGs represent tractable vulnerabilities in precision oncology. By bridging mechanistic insights with clinical implications, this review positions SGs as a promising frontier in overcoming cancer therapy resistance.
应激颗粒（SGs）是动态、无膜的细胞器，在应激条件下形成，并在翻译调控、RNA代谢和细胞存活中发挥关键作用。在癌症中，应激颗粒日益被视为治疗耐药性的核心介质，使恶性细胞能够逃避凋亡、重编程代谢并调节免疫应答。理解健康细胞与癌细胞中应激颗粒动力学的机制与临床意义，对于精准肿瘤学中靶向这些颗粒具有重要潜力。本综述整合了当前关于化疗药物、致癌信号通路及肿瘤微环境应激源如何促进应激颗粒形成的知识，以及不同肿瘤类型中应激颗粒动力学改变的证据。我们进一步强调肿瘤微环境内应激颗粒成分的上调如何塑造癌细胞行为与适应性，以及应激颗粒与其他生物分子凝聚体之间的交互作用如何促成耐药性。最后，我们讨论了针对应激颗粒的新兴治疗策略，包括激酶抑制剂和应激颗粒动力学调节剂，并提出应激颗粒可作为精准肿瘤学中可干预的脆弱环节。通过将机制性见解与临床意义相联结，本综述将应激颗粒定位为克服癌症治疗耐药性的重要前沿领域。
Stress Granule-Driven Resistance in Cancer: Mechanisms and Emerging Strategies
肿瘤(癌症)患者之家