Colorectal cancer (CRC) is a global health concern and a leading cause of death worldwide. The disease’s course and response to treatment are significantly influenced by its heterogeneity, both within a single lesion and between primary and metastatic sites. Biomarkers, such as mutations inKRAS,NRAS, andBRAF, provide valuable guidance for treatment decisions in patients with metastatic CRC. While high concordance exists between mutational status in primary and metastatic lesions, some heterogeneity may be present. Circulating tumor DNA (ctDNA) analysis has proven invaluable in identifying genetic heterogeneity and predicting prognosis inRAS-mutated metastatic CRC patients. Tumor heterogeneity can arise from genetic and non-genetic factors, affecting tumor development and response to therapy. To comprehend and address clonal evolution and intratumoral heterogeneity, comprehensive genomic studies employing techniques such as next-generation sequencing and computational analysis are essential. Liquid biopsy, notably through analysis of ctDNA, enables real-time clonal evolution and treatment response monitoring. However, challenges remain in standardizing procedures and accurately characterizing tumor subpopulations. Various models elucidate the origin of CRC heterogeneity, highlighting the intricate molecular pathways involved. This review focuses on intrapatient cancer heterogeneity and genetic clonal evolution in metastatic CRC, with an emphasis on clinical applications.
结直肠癌是全球性的健康问题，也是世界范围内主要致死原因之一。该疾病的发展进程及治疗反应明显受其异质性影响，这种异质性既存在于单个病灶内部，也表现于原发灶与转移灶之间。KRAS、NRAS和BRAF等基因突变作为生物标志物，为转移性结直肠癌患者的治疗决策提供了重要指导。虽然原发灶与转移灶的突变状态通常高度一致，但仍可能存在一定的异质性。循环肿瘤DNA分析在识别遗传异质性和预测RAS突变转移性结直肠癌患者预后方面已被证明具有重要价值。肿瘤异质性可能源于遗传与非遗传因素，影响肿瘤发展及治疗反应。为理解和应对克隆进化与瘤内异质性，采用新一代测序与计算分析技术的全面基因组研究至关重要。液体活检（特别是通过ctDNA分析）能够实时监测克隆进化与治疗反应，但目前仍面临操作流程标准化及精准表征肿瘤亚群等挑战。多种理论模型阐释了结直肠癌异质性的起源，揭示了其中涉及的复杂分子通路。本综述聚焦于转移性结直肠癌的患者内癌症异质性与遗传克隆进化，着重探讨其临床应用价值。
肿瘤(癌症)患者之家