Huang Zhe, Yang Mingli
The Department of 11th General Surgery, Minimally Invasive Colorectal Hernia Unit, Shengjing Hospital of China Medical University, Shenyang, China.
The Department of 3Oncology, Gastrointestinal Cancer Unit, Shengjing Hospital of China Medical University, Shenyang, China.
Front Oncol. 2022 Apr 6;12:852927. doi: 10.3389/fonc.2022.852927. eCollection 2022.
Colorectal cancer (CRC), a leading cause of cancer-related mortalities globally, results from the accumulation of multiple genetic and epigenetic alterations in the normal colonic and rectum epithelium, leading to the progression from colorectal adenomas to invasive carcinomas. Almost half of CRC patients will develop metastases in the course of the disease and most patients with metastatic CRC are incurable. Particularly, the 5-year survival rate of patients with stage 4 CRC at diagnosis is less than 10%. Although genetic understanding of these CRC tumors and paired metastases has led to major advances in elucidating early driver genes responsible for carcinogenesis and metastasis, the pathophysiological contribution of transcriptional and epigenetic aberrations in this malignancy which influence many central signaling pathways have attracted attention recently. Therefore, treatments that could affect several different molecular pathways may have pivotal implications for their efficacy. In this review, we summarize our current knowledge on the molecular network of CRC, including cellular signaling pathways, CRC microenvironment modulation, epigenetic changes, and CRC biomarkers for diagnosis and predictive/prognostic use. We also provide an overview of opportunities for the treatment and prevention strategies in this field.
结直肠癌（CRC）是全球癌症相关死亡的主要原因之一，它源于正常结肠和直肠上皮细胞中多种基因和表观遗传改变的积累，导致从结直肠腺瘤发展为浸润性癌。几乎一半的CRC患者在疾病过程中会发生转移，大多数转移性CRC患者无法治愈。特别是，诊断时处于4期CRC的患者5年生存率低于10%。尽管对这些CRC肿瘤及其配对转移灶的遗传学认识已在阐明负责致癌和转移的早期驱动基因方面取得了重大进展，但这种恶性肿瘤中转录和表观遗传异常对许多核心信号通路的病理生理贡献最近引起了关注。因此，能够影响几种不同分子途径的治疗方法可能对其疗效具有关键意义。在这篇综述中，我们总结了目前关于CRC分子网络的知识，包括细胞信号通路、CRC微环境调节、表观遗传变化以及用于诊断和预测/预后的CRC生物标志物。我们还概述了该领域治疗和预防策略的机会。
