结直肠癌涉及的信号通路：发病机理和靶向治疗
Signaling pathways involved in colorectal cancer: pathogenesis and targeted therapy
影响因子:52.70000
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
摘要
结直肠癌（CRC）仍然是全球与癌症相关死亡率的主要原因之一。它的复杂性受到控制细胞增殖，生存，分化和凋亡的各种信号转导网络的影响。 CRC的发病机理证明了这些信号级联反应的失调，这最终导致结肠上皮的恶性转化。这篇综述旨在剖析与CRC有关的基础信号传导机制，以阐明肿瘤演化和进展的普遍原则。我们讨论了CRC的分子标志，包括CRC的基因组，表观基因组和微生物特征，以突出信号转导在肿瘤过程的编排中的作用。同时，我们回顾了CRC中有针对性和免疫疗法的出现，评估了它们对当前临床景观的影响。通过加深对致癌信号传导的理解，已经为这些疗法的发展提供了信息，从而导致可以在药理上剥削的这些网络中的关键节点。此外，我们探索了整合AI以增强治疗性靶向和患者分层的精度的潜力，并强调了它们在个性化医学中的作用。总而言之，我们的综述捕获了CRC发病机理中异常信号传导与通过有针对性的治疗策略来抵消这些变化的努力之间的动态相互作用，最终旨在为改善结直肠癌的预后和个性化治疗方式铺平道路。
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.