结直肠癌中的信号通路：发病机制与靶向治疗
Signaling pathways involved in colorectal cancer: pathogenesis and targeted therapy
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影响因子:52.7
分区:医学1区 Top / 生化与分子生物学1区 细胞生物学1区
发表日期:2024 Oct 07
作者:
Qing Li, Shan Geng, Hao Luo, Wei Wang, Ya-Qi Mo, Qing Luo, Lu Wang, Guan-Bin Song, Jian-Peng Sheng, Bo Xu
DOI:
10.1038/s41392-024-01953-7
摘要
结直肠癌（CRC）仍然是全球癌症相关死亡的主要原因之一。其复杂性受到多种信号转导网络的影响，这些网络调控细胞增殖、生存、分化和凋亡。CRC的发病机制反映了这些信号级联反应的失调，导致结肠上皮细胞的恶性转化。本文旨在解析CRC中关键的信号传导机制，揭示肿瘤发生与发展的基本原则。我们讨论了CRC的分子标志物，包括基因组、表观遗传和微生物特征，强调信号转导在肿瘤发生过程中的调控作用。同时，回顾了针对CRC的靶向和免疫治疗的最新进展，评估其在临床中的影响。随着对癌基因信号通路的深入理解，识别出关键节点，为药物开发提供了基础。此外，本文还探讨了整合人工智能以提升治疗靶向的精准性和患者分层的潜力，强调其在个性化治疗中的作用。总之，本文捕捉了CRC发病机制中异常信号转导的动态变化及其靶向治疗策略的协同作用，为改善预后和实现个体化治疗提供了理论基础。
Abstract
Colorectal cancer (CRC) remains one of the leading causes of cancer-related mortality worldwide. Its complexity is influenced by various signal transduction networks that govern cellular proliferation, survival, differentiation, and apoptosis. The pathogenesis of CRC is a testament to the dysregulation of these signaling cascades, which culminates in the malignant transformation of colonic epithelium. This review aims to dissect the foundational signaling mechanisms implicated in CRC, to elucidate the generalized principles underpinning neoplastic evolution and progression. We discuss the molecular hallmarks of CRC, including the genomic, epigenomic and microbial features of CRC to highlight the role of signal transduction in the orchestration of the tumorigenic process. Concurrently, we review the advent of targeted and immune therapies in CRC, assessing their impact on the current clinical landscape. The development of these therapies has been informed by a deepening understanding of oncogenic signaling, leading to the identification of key nodes within these networks that can be exploited pharmacologically. Furthermore, we explore the potential of integrating AI to enhance the precision of therapeutic targeting and patient stratification, emphasizing their role in personalized medicine. In summary, our review captures the dynamic interplay between aberrant signaling in CRC pathogenesis and the concerted efforts to counteract these changes through targeted therapeutic strategies, ultimately aiming to pave the way for improved prognosis and personalized treatment modalities in colorectal cancer.