Chen Hao, Luo Wenhao, Lu Xiaoyue, Zhang Taiping
Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China.
Peking Union Medical College, Beijing, China.
Heliyon. 2023 Oct 17;9(11):e20969. doi: 10.1016/j.heliyon.2023.e20969. eCollection 2023 Nov.
Pancreatic ductal adenocarcinoma (PDAC) is an extremely life-threatening malignancy with a relatively unfavorable prognosis. The early occurrence of metastasis and local recurrence subsequent to surgery contribute to the poor survival rates of PDAC patients, thereby limiting the effectiveness of surgical intervention. Additionally, the desmoplastic and immune-suppressive tumor microenvironment of PDAC diminishes its responsiveness to conventional treatment modalities such as chemotherapy, radiotherapy, and immunotherapy. Therefore, it is imperative to identify novel therapeutic targets for PDAC treatment. Chemical modifications are prevalent in various types of RNA and exert significant influence on their structure and functions. RNA modifications, exemplified by mA, mC, mA, and Ψ, have been identified as general regulators of cellular functions. The abundance of specific modifications, such as mA, has been correlated with cell proliferation, invasion, migration, and patient prognosis in PDAC. Pre-clinical data has indicated that manipulating RNA modification regulators could enhance the efficacy of chemotherapy, radiotherapy, and immunotherapy. Therefore, targeting RNA modifications in conjunction with current adjuvant or neoadjuvant therapy holds promise. The objective of this review is to provide a comprehensive overview of RNA modifications in PDAC treatment, encompassing their behaviors, mechanisms, and potential treatment targets. Therefore, it aims to stimulate the development of novel therapeutic approaches and future clinical trials.
胰腺导管腺癌（PDAC）是一种极具生命威胁的恶性肿瘤，预后相对较差。手术后早期发生转移和局部复发导致PDAC患者生存率较低，从而限制了手术干预的效果。此外，PDAC的促结缔组织增生和免疫抑制性肿瘤微环境降低了其对化疗、放疗和免疫治疗等传统治疗方式的反应性。因此，必须为PDAC治疗确定新的治疗靶点。化学修饰在各类RNA中普遍存在，并对其结构和功能产生重大影响。以m⁶A、m⁵C、m¹A和Ψ为代表的RNA修饰已被确定为细胞功能的一般调节因子。特定修饰（如m⁶A）的丰度与PDAC中的细胞增殖、侵袭、迁移及患者预后相关。临床前数据表明，调控RNA修饰调节因子可提高化疗、放疗和免疫治疗的疗效。因此，将RNA修饰作为靶点并结合当前的辅助或新辅助治疗具有前景。本综述的目的是全面概述PDAC治疗中的RNA修饰，包括其表现、机制和潜在治疗靶点。因此，其旨在推动新型治疗方法的发展及未来的临床试验。
