胰腺癌细胞外吉西他滨耐药机制的研究进展

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...

Advances in research of extracellular mechanisms underlying gemcitabine resistance in pancreatic cancer

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.