摘要
胰腺癌是预后最差的实体恶性肿瘤,其中约90%是胰腺导管腺癌(pancreatic ductal adenocarcinoma,PDAC).尽管手术切除是唯一可能治愈PDAC的手段,但术后总体生存率不容乐观.因此,以吉西他滨(gemcitabine,GEM)为基础的化疗仍是PDAC最重要的治疗选择之一.然而,GEM单药治疗晚期PDAC的生存期改善十分有限,其关键原因在于GEM耐药.GEM耐药的机制复杂且不明确.肿瘤微环境(tumor microenvironment,TME)中广泛而致密的纤维间质是PDAC的重要特征.越来越多的证据显示,纤维化TME不仅是肿瘤生长、扩散的积极参与者,更是诱导GEM耐药的贡献者.本文将重点从PDAC细胞外途径对GEM化疗耐药的主要细胞和分子机制研究进展进行综述,讨论潜在的GEM化疗增敏策略,以期提高化疗有效率,改善PDAC的总体预后.
Pancreatic cancer is a solid malignant tumor with the worst prognosis worldwide,and about 90%of cases are pancreatic ductal adenocarcinoma(PDAC).Although surgical resection is the only potential way to cure PDAC,the overall survival rate after surgery is still not optimistic.Consequently,gemcitabine(GEM)-based chemotherapy is still one of the most important treatment options for PDAC.However,the survival improvement by GEM monotherapy for advanced PDAC is very limited,and GEM resistance is the key reason.The mechanism underlying gemcitabine resistance is complex and still unclear in PDAC.The extensive and dense fibrous mesenchyme in the tumor microenvironment(TME)is an important feature of PDAC.More and more evidence has shown that TME is not only an active participant in tumor growth and spread,but also a contributor to the induction of GEM resistance.This article will review the recent advances in the understanding of the cellular and molecular mechanisms underlying GEM resistance in PDAC,and discuss potential GEM chemosensitization strategies,in order to improve the effective rate of chemotherapy and the outcome.
作者
顾宗廷
李宗泽
王成锋
Zong-Ting Gu;Zong-Ze Li;Cheng-feng Wang(State Key Laboratory of Molecular Oncology&Department of Pancreatic and Gastric Surgery,National Cancer Center/Cancer Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100021,China)
出处
《世界华人消化杂志》
CAS
2021年第8期421-434,共14页
World Chinese Journal of Digestology
基金
国家自然科学基金面上项目,No.81972314
中国医学科学院医学与健康科技创新工程,No.2016-I2M-1-001.
关键词
胰腺癌
胰腺导管腺癌
吉西他滨
肿瘤微环境
化疗耐药
Pancreatic cancer
Pancreatic ductal adenocarcinoma
Gemcitabine
Tumor microenvironment
Chemoresistance
