家族性腺瘤性息肉病的化学预防药物进展与展望

Progress and prospect in chemoprevention of familial adenomatous polyposis

家族性腺瘤性息肉病(familial adenomatous polyposis,FAP)是一种主要由APC基因胚系突变引起的遗传性结直肠癌综合征,表现为高发的结直肠腺瘤和接近100%的终身结直肠癌风险。早期内镜下筛查和预防性全结(直)肠切除术是FAP目前主要治疗方法。但该手术无法预防结肠外疾病,如十二指肠肿瘤、硬纤维瘤和甲状腺癌等,且对患者造成极大的心理和生理负担,影响生活质量。近年来,研究集中在化学预防药物上,目的是延缓疾病进展和推延肠道手术切除时机,同时减缓结肠外疾病的发展,降低手术相关硬纤维瘤的发生率。目前,FAP的化学预防还处于早期阶段,尚无药物被批准,未来需基于APC胚系突变的具体突变位点来指导安全有效的药物预防和治疗策略。本文旨在回顾FAP化学预防的相关文献和研究进展,以期对其有全面了解并为未来开展临床试验提供方向。

Familial adenomatous polyposis(FAP)is a hereditary colorectal cancer syndrome primarily caused by mutations in the APC gene,characterized by a high incidence of colorectal adenomas and a nearly 100%lifetime risk of colorectal cancer.Early endoscopic screening and prophylactic colectomy are currently the main treatment methods for FAP.However,this surgery cannot prevent extracolonic diseases such as duodenal tumors,desmoid tumors,and thyroid cancer,and it imposes a significant psychological and physiological burden on patients,affecting their quality of life.In recent years,research has focused on chemopreventive drugs with the aim of delaying disease progression and the need for colectomy,while also slowing the development of extracolonic diseases and reducing the incidence of surgery-related desmoid tumors.Currently,chemoprevention of FAP is still in the early stages,with no drugs approved yet,necessitating safer and more effective drug and treatment strategies based on genetic background.This paper aims to review the relevant literature and research trends of chemoprevention of FAP,to have a comprehensive understanding of it and provide direction for future clinical trials.