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.

放射是癌症治疗的关键支柱，通过各种直接和间接机制发挥其抗肿瘤 DNA 损伤作用。放射治疗已成为多种癌症类型的有效治疗方式，提供治愈性和姑息性治疗；然而，对治疗的抵抗仍然是一个根本限制。虽然癌细胞死亡是任何抗肿瘤治疗的理想结果，但辐射会诱发多种反应，包括细胞凋亡、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，自噬作为一种传统的细胞保护机制，是化疗和放疗造成损伤的“第一”反应者。以自噬本质上具有细胞保护作用为前提而开发的范式为当前旨在通过使用自噬抑制剂使癌细胞放射增敏的临床试验提供了理论基础；然而，这些都未能产生一致的结果。进一步深入临床前研究，自噬实际上已被证明采取多种、有时是相反的形式，例如以细胞毒性或非保护性方式发挥作用，这可能是导致临床结果不一致的部分原因。此外，自噬可以具有促肿瘤和抗肿瘤作用，同时还具有重要的免疫调节功能。衰老通常与自噬同时发生，辐射也是如此。辐射诱导的衰老之后经常会出现细胞子集的增殖恢复阶段，并且已被提议作为肿瘤休眠模型，这可能会导致对治疗的抵抗，并可能导致疾病复发。 衰老诱导通常伴随着独特的分泌表型，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谱。对衰老细胞具有选择性细胞毒性的新型疗法（senolytics）可能被证明可以通过延迟患者疾病复发来延长缓解时间。对放射的主要反应的准确评估可能提供潜在的靶点，可以操纵这些靶点以获得治疗效果，使癌细胞对放疗敏感，同时不伤害正常组织。