结肠癌转移机制及其治疗研究进展

Advances in the Mechanism of Colorectal Cancer Metastasis and its Treatment

结肠癌是世界范围内最常见的癌症之一,近几十年来,结肠癌在中国的发病率和死亡率迅速上升,转移是导致结肠癌患者死亡的主要原因,癌症的转移是指癌细胞通过血液循环或淋巴系统从原部位扩散到其他器官或组织。为了在远处的器官或组织上定植,进入循环的肿瘤细胞必须通过许多障碍。具有侵袭性和运动性的肿瘤细胞需要从原发肿瘤部位进入循环系统,接着浸润远处的组织,逃避免疫防御,适应支持的龛位,作为具有肿瘤启动能力的干细胞存活于远处器官和组织,最终引起恶性程度较高的远端转移。为了更好地预防和治疗转移性结肠癌,需要清晰地揭示结肠癌转移过程中的分子生物学机制,文章从上皮细胞间充质转化过程、肿瘤微环境的作用以及肿瘤干细胞在远端转移灶的生长3个方面总结了结肠癌转移机制研究的最新进展,其中重点对TGF-β在结肠癌转移中的作用进行了总结,TGF-β在上皮间充质转化过程对结肠癌的转移有一定的促进作用,且能够将肿瘤微环境中的组分之间的联系起来促进结肠癌转移,同时在支持肿瘤干细胞的生长和存活方面发挥作用。并且从一线治疗方案、靶向药物联用、潜在的治疗靶点等3个方面介绍了转移性结肠癌的治疗研究进展,主要介绍了以TGF-β为靶点的一些小分子抑制剂的研究进展,以期为转移性结肠癌相关研究及临床治疗提供参考。

Colorectal cancer is one of the most common cancers worldwide.In recent decades,incidence and mortality of colorectal cancer in China have rapidly increased.Metastasis is the main cause of death in patients with colorectal cancer.Metastasis of cancer is the spread of cancer cells from their original site to other organs or tissues through the circulatory system or lymphatic system.To colonize distant organs or tissues,tumor cells entering the circulation must overcome a number of barriers.Invasive and motional tumor cells need to enter the circulatory system from the primary tumor site,then infiltrate distant tissues,evade immune defenses,adapt to supporting niche,and survive in distant organs and tissues as stem cells with tumor-initiating ability,eventually causing distal metastasis with high malignancy.To better prevent and treat metastatic colorectal cancer,it is necessary to clearly reveal the molecular biological mechanism of metastatic colorectal cancer.This review summarized the latest research progresses of colorectal cancer metastasis mechanism from three aspects:epithelium-mesenchymal transformation process,the role of tumor microenvironment,and the growth course of tumor stem cells in the remote metastasis.This article focuses on the role of TGF-βin colorectal cancer metastasis was summarized,TGF-βin the process of epithelial mesenchymal transformation on colorectal cancer metastasis has a certain promotion effect,and can link components in the tumor microenvironment such as angiogenesis and tumor-associated fibroblasts to promote colorectal cancer metastasis,at the same time in support of tumor stem cell growth and survival plays an important role.In addition,the research progresses in the treatment of metastatic colorectal cancer were introduced from three aspects,including first-line treatment,targeted drug combination and potential therapeutic targets.And the research progress of some small molecule inhibitors targeting TGF-βwere mainly introduced,in order to provide reference for the related research and clinical treatment of metastatic colorectal cancer.