肿瘤细胞治疗研究
英文原题：Gastrointestinal cancer: molecular pathogenesis and targeted therapy.
Gastrointestinal cancer: molecular pathogenesis and targeted therapy.
胃肠道（GI）癌症构成了重大的全球健康负担，其驱动因素是复杂的分子改变和微环境相互作用。
胃肠道（GI）肿瘤构成了重大的全球健康负担，其驱动因素为复杂的分子改变和微环境相互作用。分子发病机制的进展已阐明反复出现的驱动基因突变，如 KRAS、TP53 和 APC，以及失调的信号通路，包括 Wnt、RAS-MAPK 和 PI3K-AKT，这些共同构成了肿瘤发生和进展的基础。与遗传改变相辅相成，表观遗传改变——如 DNA 高甲基化、组蛋白修饰和调控性非编码 RNA——通过重塑染色质结构和基因表达，进一步促进恶性演化。这些机制不仅促进不受控制的增殖，还通过动态修饰肿瘤微环境（TME）来强化治疗耐药性。分子分型工作，包括胃癌（GC）的癌症基因组图谱（TCGA）分类和结直肠癌（CRC）的共识分子亚型（CMS），已描绘出疾病异质性，揭示了不同的致病途径，并使得预后分层更加精细。这些见解为诊断技术和靶向干预提供了生物学依据。例如，抗 EGFR 和抗 VEGF 单克隆抗体分别破坏致癌信号和肿瘤血管生成，并已在选定的患者群体中显示出显著的临床疗效。与此同时，免疫治疗已成为肿瘤学中一种变革性的治疗模式。靶向 PD-1/PD-L1 和 CTLA-4 的免疫检查点抑制剂重新激活抗肿瘤免疫，并已重塑了多种 GI 恶性肿瘤的标准治疗协议。除传统免疫疗法外，CAR-T细胞疗法和基于新抗原的疫苗等创新策略正在积极研究中。这些方法旨在克服免疫逃逸机制并增强肿瘤特异性靶向，为耐药或晚期疾病患者带来希望。本综述全面分析了GI癌症不断演变的分子格局以及相应的靶向和免疫治疗药物的开发。它强调了机制发现与临床转化的平衡整合，突显了它们在推进精准肿瘤学和改善生存结局方面的协同作用。
Gastrointestinal (GI) cancers pose a significant global health burden, driven by complex molecular alterations and microenvironmental interactions. Advances in molecular pathogenesis have elucidated recurrent driver gene mutations, such as KRAS, TP53, and APC, alongside dysregulated signaling pathways including Wnt, RAS-MAPK, and PI3K-AKT, which collectively underpin tumor initiation and progression. Complementing genetic changes, epigenetic alterations-such as DNA hypermethylation, histone modifications, and regulatory non-coding RNAs-further contribute to malignant evolution by reshaping chromatin architecture and gene expression. These mechanisms not only promote uncontrolled proliferation but also reinforce therapeutic resistance by dynamically modifying the tumor microenvironment (TME). Molecular subtyping efforts, including The Cancer Genome Atlas (TCGA) classification for gastric cancer (GC) and the Consensus Molecular Subtypes (CMS) for colorectal cancer (CRC), have delineated disease heterogeneity, revealing distinct pathogenic pathways and enabling refined prognostic stratification. Such insights provide the biological rationale for diagnostic techniques and targeted interventions. For instance, anti-EGFR and anti-VEGF monoclonal antibodies disrupt oncogenic signaling and tumor angiogenesis, respectively, and have demonstrated substantial clinical efficacy in selected patient populations. In parallel, immunotherapy has emerged as a transformative modality in oncology. Immune checkpoint inhibitors targeting PD-1/PD-L1 and CTLA-4 reinvigorate antitumor immunity and have reshaped standard-of-care protocols for several GI malignancies. Beyond conventional immunotherapies, innovative strategies such as CAR-T cell therapy and neoantigen-based vaccines are being actively investigated. These approaches aim to overcome immune evasion mechanisms and enhance tumor-specific targeting, offering promise for patients with resistant or advanced disease. This review comprehensively analyzes the evolving molecular landscape of GI cancers and the corresponding development of targeted and immunotherapeutic agents. It highlights a balanced integration of mechanistic discovery and clinical translation, underscoring their synergistic roles in advancing precision oncology and improving survival outcomes.
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