Radiation is a critical pillar in cancer therapeutics, exerting its anti-tumor DNA-damaging effects through various direct and indirect mechanisms. Radiation has served as an effective mode of treatment for a number of cancer types, providing both curative and palliative treatment; however, resistance to therapy persists as a fundamental limitation. While cancer cell death is the ideal outcome of any anti-tumor treatment, radiation induces several responses, including apoptotic cell death, mitotic catastrophe, autophagy and senescence, where autophagy and senescence may promote cell survival. In most cases, autophagy, a conventionally cytoprotective mechanism, is a “first” responder to damage incurred from chemotherapy and radiation treatment. The paradigm developed on the premise that autophagy is cytoprotective in nature has provided the rationale for current clinical trials designed with the goal of radiosensitizing cancer cells through the use of autophagy inhibitors; however, these have failed to produce consistent results. Delving further into pre-clinical studies, autophagy has actually been shown to take diverse, sometimes opposing, forms, such as acting in a cytotoxic or nonprotective fashion, which may be partially responsible for the inconsistency of clinical outcomes. Furthermore, autophagy can have both pro- and anti-tumorigenic effects, while also having an important immune modulatory function. Senescence often occurs in tandem with autophagy, which is also the case with radiation. Radiation-induced senescence is frequently followed by a phase of proliferative recovery in a subset of cells and has been proposed as a tumor dormancy model, which can contribute to resistance to therapy and possibly also disease recurrence. Senescence induction is often accompanied by a unique secretory phenotype that can either promote or suppress immune functions, depending on the expression profile of cytokines and chemokines. Novel therapeutics selectively cytotoxic to senescent cells (senolytics) may prove to prolong remission by delaying disease recurrence in patients. Accurate assessment of primary responses to radiation may provide potential targets that can be manipulated for therapeutic benefit to sensitize cancer cells to radiotherapy, while sparing normal tissue.

辐射是癌症治疗中的重要支柱，它通过各种直接和间接机制发挥其抗肿瘤DNA破坏作用。放射线已成为多种癌症的有效治疗方式，提供了治愈性和姑息性治疗。然而，对治疗的抵抗仍然是基本限制。尽管癌细胞死亡是任何抗肿瘤治疗的理想结果，但放射线会诱导多种反应，包括凋亡性细胞死亡，有丝分裂灾难，自噬和衰老，其中自噬和衰老可能促进细胞存活。在大多数情况下，自噬是一种常规的细胞保护机制，是化学疗法和放射治疗所造成损害的“第一反应”。在自噬本质上具有细胞保护作用的前提下开发的范例为目前的临床试验提供了理论依据，旨在通过使用自噬抑制剂对癌细胞进行放射增敏。但是，这些未能产生一致的结果。进一步研究临床前研究，自噬实际上已显示出多种形式，有时是相反的形式，例如以细胞毒性或非保护性方式起作用，这可能部分导致临床结果的不一致。此外，自噬可以同时具有促肿瘤作用和抗肿瘤作用，同时还具有重要的免疫调节功能。自噬常常与衰老同时发生，放射线也是如此。辐射诱发的衰老通常伴随着细胞亚群的增殖恢复阶段，并已被提议作为肿瘤休眠模型，其可导致对治疗的抵抗以及可能的疾病复发。衰老诱导通常伴随着独特的分泌表型，其可以促进或抑制免疫功能，具体取决于细胞因子和趋化因子的表达情况。对衰老细胞（senolytics）具有选择性细胞毒性的新型疗法可能会通过延迟患者的疾病复发来延长其缓解时间。对放射线主要反应的准确评估可能会提供可能的靶标，可以对该靶标进行操作以获得治疗益处，从而使癌细胞对放射疗法敏感，同时保留正常组织。可能会导致对治疗的抵抗力，甚至可能导致疾病复发。衰老诱导通常伴随着独特的分泌表型，其可以促进或抑制免疫功能，具体取决于细胞因子和趋化因子的表达情况。对衰老细胞（senolytics）具有选择性细胞毒性的新型疗法可能会通过延迟患者的疾病复发来延长其缓解时间。对放射线主要反应的准确评估可能会提供可能的靶标，可以对该靶标进行操作以获得治疗益处，从而使癌细胞对放射疗法敏感，同时保留正常组织。可能会导致对治疗的抵抗力，甚至可能导致疾病复发。衰老诱导通常伴随着独特的分泌表型，该表型可以促进或抑制免疫功能，具体取决于细胞因子和趋化因子的表达情况。对衰老细胞（senolytics）具有选择性细胞毒性的新型疗法可能会通过延迟患者的疾病复发来延长其缓解时间。对放射线主要反应的准确评估可能会提供可能的靶标，可以对该靶标进行操作以获得治疗益处，从而使癌细胞对放射疗法敏感，同时保留正常组织。取决于细胞因子和趋化因子的表达情况。对衰老细胞（senolytics）具有选择性细胞毒性的新型治疗药物可通过延迟患者的疾病复发来延长其缓解时间。对放射线主要反应的准确评估可能会提供可能的靶标，可以对该靶标进行操作以获得治疗益处，从而使癌细胞对放射疗法敏感，同时保留正常组织。取决于细胞因子和趋化因子的表达情况。对衰老细胞（senolytics）具有选择性细胞毒性的新型疗法可能会通过延迟患者的疾病复发来延长其缓解时间。对放射线主要反应的准确评估可能会提供可能的靶标，可以对该靶标进行操作以获得治疗益处，从而使癌细胞对放射疗法敏感，同时保留正常组织。