Department of Pancreatic and Hepatobiliary Surgery, Fudan University Shanghai Cancer Center, 270 Dongan Road, Shanghai, 200032, People's Republic of China.
Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, People's Republic of China.
Cell Mol Life Sci. 2018 Mar;75(6):1001-1012. doi: 10.1007/s00018-017-2678-7. Epub 2017 Oct 9.
Pancreatic ductal adenocarcinoma (PDAC) is among the most devastating human malignancies, with approximately 20-30% of PDAC patients receiving the surgical resection with curative intent. Although many studies have focused on finding ideal "drug chaperones" that facilitate and/or potentiate the effects of gemcitabine (GEM) in pancreatic cancer, a significant benefit in overall survival could not be demonstrated for any of these combination therapies in PDAC. Given that pancreatic cancer is characterized by desmoplasia and the dual biological roles of stroma in pancreatic cancer, we reassess the importance of stroma in GEM-based therapeutic approaches in light of current findings. This review is focused on understanding the role of stromal components in the extrinsic resistance to GEM and whether anti-stroma therapies have a positive effect on the GEM delivery. This work contributes to the development of novel and promising combination GEM-based regimens that have achieved significant survival benefits for the patients with pancreatic cancer.
胰腺导管腺癌 (PDAC) 是最具破坏性的人类恶性肿瘤之一，约有 20-30%的 PDAC 患者接受了有治愈意图的手术切除。尽管许多研究都集中在寻找理想的“药物伴侣”上，以促进和/或增强吉西他滨 (GEM) 在胰腺癌中的作用，但在任何这些联合治疗中都无法证明对总体生存率有显著益处。鉴于胰腺癌的特征是纤维增生和基质在胰腺癌中的双重生物学作用，我们根据当前的发现重新评估基质在基于 GEM 的治疗方法中的重要性。这篇综述的重点是了解基质成分在 GEM 耐药中的外在作用，以及抗基质治疗是否对 GEM 的传递有积极影响。这项工作有助于开发新的、有前途的基于 GEM 的联合方案，为胰腺癌患者带来了显著的生存获益。
