抗基质治疗能否提高外在耐药性以提高胰腺癌中吉西他滨的疗效？
Do anti-stroma therapies improve extrinsic resistance to increase the efficacy of gemcitabine in pancreatic cancer?
机构信息
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.
出版信息
Cell Mol Life Sci. 2018 Mar;75(6):1001-1012. doi: 10.1007/s00018-017-2678-7. Epub 2017 Oct 9.
Abstract
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.
摘要
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。
相似文献
1
Do anti-stroma therapies improve extrinsic resistance to increase the efficacy of gemcitabine in pancreatic cancer?抗基质治疗能否提高外在耐药性以提高胰腺癌中吉西他滨的疗效？
Cell Mol Life Sci. 2018 Mar;75(6):1001-1012. doi: 10.1007/s00018-017-2678-7. Epub 2017 Oct 9.
2
Nano albumin bound-paclitaxel in pancreatic cancer: Current evidences and future directions.纳米白蛋白结合型紫杉醇在胰腺癌中的应用：当前证据与未来方向。
World J Gastroenterol. 2017 Aug 28;23(32):5875-5886. doi: 10.3748/wjg.v23.i32.5875.
3
Signal Transducer and Activator of Transcription 3, Mediated Remodeling of the Tumor Microenvironment Results in Enhanced Tumor Drug Delivery in a Mouse Model of Pancreatic Cancer.信号转导子和转录激活子 3 通过介导肿瘤微环境的重塑增强了胰腺癌小鼠模型中的肿瘤药物递送。
Gastroenterology. 2015 Dec;149(7):1932-1943.e9. doi: 10.1053/j.gastro.2015.07.058. Epub 2015 Aug 7.
4
Superior therapeutic efficacy of nab-paclitaxel over cremophor-based paclitaxel in locally advanced and metastatic models of human pancreatic cancer.在人胰腺癌局部晚期和转移模型中，纳米白蛋白结合型紫杉醇对比基于聚氧乙烯蓖麻油的紫杉醇具有更高的治疗效果。
Br J Cancer. 2016 Aug 9;115(4):442-53. doi: 10.1038/bjc.2016.215. Epub 2016 Jul 21.
5
Inhibiting tumor necrosis factor-alpha diminishes desmoplasia and inflammation to overcome chemoresistance in pancreatic ductal adenocarcinoma.抑制肿瘤坏死因子-α可减轻促结缔组织增生反应和炎症，从而克服胰腺导管腺癌的化疗耐药性。
Oncotarget. 2016 Dec 6;7(49):81110-81122. doi: 10.18632/oncotarget.13212.
6
Computational modeling of pancreatic cancer patients receiving FOLFIRINOX and gemcitabine-based therapies identifies optimum intervention strategies.基于 FOLFIRINOX 和吉西他滨治疗的胰腺癌患者的计算模型确定最佳干预策略。
PLoS One. 2019 Apr 26;14(4):e0215409. doi: 10.1371/journal.pone.0215409. eCollection 2019.
7
Modified gemcitabine plus nab-paclitaxel regimen in advanced pancreatic ductal adenocarcinoma.改良吉西他滨联合 nab-紫杉醇方案治疗晚期胰腺导管腺癌。
Cancer Med. 2020 Aug;9(15):5406-5415. doi: 10.1002/cam4.3229. Epub 2020 Jun 9.
8
Interstitial lung disease in advanced pancreatic ductal adenocarcinoma patients treated with gemcitabine and nab-paclitaxel combination therapy: a retrospective analysis.吉西他滨联合 nab-紫杉醇治疗晚期胰腺导管腺癌患者的间质性肺病：回顾性分析。
Cancer Chemother Pharmacol. 2020 Mar;85(3):517-523. doi: 10.1007/s00280-019-03983-3. Epub 2019 Nov 5.
9
The absence of class III β-tubulin is predictive of a favorable response to nab-paclitaxel and gemcitabine in patients with unresectable pancreatic ductal adenocarcinoma.III 类β-微管蛋白缺失可预测不可切除的胰腺导管腺癌患者对 nab-紫杉醇和吉西他滨的治疗反应良好。
Hum Pathol. 2018 Apr;74:92-98. doi: 10.1016/j.humpath.2018.01.009. Epub 2018 Jan 12.
10
Response and Survival Associated With First-line FOLFIRINOX vs Gemcitabine and nab-Paclitaxel Chemotherapy for Localized Pancreatic Ductal Adenocarcinoma.一线 FOLFIRINOX 方案与吉西他滨联合 nab-紫杉醇化疗治疗局限性胰腺导管腺癌的反应和生存情况。
JAMA Surg. 2020 Sep 1;155(9):832-839. doi: 10.1001/jamasurg.2020.2286.
引用本文的文献
1
Nanotension Relief Agent Enhances Tissue Penetration by Reducing Solid Stress in Pancreatic Ductal Adenocarcinoma via Rho/ROCK Pathway Inhibition.纳米张力缓解剂通过抑制Rho/ROCK通路降低胰腺导管腺癌中的固体应力来增强组织穿透能力。
Biomater Res. 2025 Apr 9;29:0173. doi: 10.34133/bmr.0173. eCollection 2025.
2
Combining gemcitabine and MSC delivering soluble TRAIL to target pancreatic adenocarcinoma and its stroma.联合吉西他滨和 MSC 递送可溶性 TRAIL 靶向胰腺腺癌及其基质。
Cell Rep Med. 2024 Aug 20;5(8):101685. doi: 10.1016/j.xcrm.2024.101685.
3
NNT-AS1 in CAFs-derived exosomes promotes progression and glucose metabolism through miR-889-3p/HIF-1α in pancreatic adenocarcinoma.CAFs 来源的外泌体中的 NNT-AS1 通过 miR-889-3p/HIF-1α 促进胰腺腺癌的进展和葡萄糖代谢。
Sci Rep. 2024 Mar 24;14(1):6979. doi: 10.1038/s41598-024-57769-6.
4
Passing of Nanocarriers across the Histohematic Barriers: Current Approaches for Tumor Theranostics.纳米载体穿越组织血液屏障：肿瘤诊疗的当前方法
Nanomaterials (Basel). 2023 Mar 23;13(7):1140. doi: 10.3390/nano13071140.
5
Leveraging Tumor Microenvironment Infiltration in Pancreatic Cancer to Identify Gene Signatures Related to Prognosis and Immunotherapy Response.利用胰腺癌中的肿瘤微环境浸润来鉴定与预后和免疫治疗反应相关的基因特征。
Cancers (Basel). 2023 Feb 24;15(5):1442. doi: 10.3390/cancers15051442.
6
Mechanical Regulation of Redox Balance via the Induction of the PIN1/NRF2/ARE Axis in Pancreatic Cancer.机械调节通过诱导胰腺癌中的 PIN1/NRF2/ARE 轴实现氧化还原平衡。
Int J Mol Sci. 2023 Feb 9;24(4):3476. doi: 10.3390/ijms24043476.
7
Membrane-camouflaged supramolecular nanoparticles for co-delivery of chemotherapeutic and molecular-targeted drugs with siRNA against patient-derived pancreatic carcinoma.用于共递送化疗药物和分子靶向药物以及针对患者来源的胰腺癌的 siRNA 的膜伪装超分子纳米颗粒。
Acta Pharm Sin B. 2022 Aug;12(8):3410-3426. doi: 10.1016/j.apsb.2022.02.007. Epub 2022 Feb 14.
8
Nanoparticle-based delivery systems modulate the tumor microenvironment in pancreatic cancer for enhanced therapy.基于纳米颗粒的递药系统调节胰腺癌的肿瘤微环境以增强治疗效果。
J Nanobiotechnology. 2021 Nov 22;19(1):384. doi: 10.1186/s12951-021-01134-6.
9
Ferroptosis: At the Crossroad of Gemcitabine Resistance and Tumorigenesis in Pancreatic Cancer.铁死亡：在胰腺癌吉西他滨耐药和肿瘤发生的十字路口。
Int J Mol Sci. 2021 Oct 10;22(20):10944. doi: 10.3390/ijms222010944.
10
TRAIL receptors are expressed in both malignant and stromal cells in pancreatic ductal adenocarcinoma.肿瘤坏死因子相关凋亡诱导配体（TRAIL）受体在胰腺导管腺癌的恶性细胞和基质细胞中均有表达。
Am J Cancer Res. 2021 Sep 15;11(9):4500-4514. eCollection 2021.
本文引用的文献
1
Fibroblast drug scavenging increases intratumoural gemcitabine accumulation in murine pancreas cancer.成纤维细胞药物清除作用增加了小鼠胰腺癌肿瘤内吉西他滨的蓄积。
Gut. 2018 Mar;67(3):497-507. doi: 10.1136/gutjnl-2016-311954. Epub 2017 Jan 10.
2
Targeting Tumor-Associated Fibroblasts for Therapeutic Delivery in Desmoplastic Tumors.靶向肿瘤相关成纤维细胞用于促结缔组织增生性肿瘤的治疗递送
Cancer Res. 2017 Feb 1;77(3):719-731. doi: 10.1158/0008-5472.CAN-16-0866. Epub 2016 Nov 18.
3
Impact of SPARC expression on outcome in patients with advanced pancreatic cancer not receiving nab-paclitaxel: a pooled analysis from prospective clinical and translational trials.SPARC表达对未接受白蛋白结合型紫杉醇的晚期胰腺癌患者预后的影响：一项来自前瞻性临床和转化试验的汇总分析
Br J Cancer. 2016 Dec 6;115(12):1520-1529. doi: 10.1038/bjc.2016.355. Epub 2016 Nov 1.
4
Metabolic plasticity in heterogeneous pancreatic ductal adenocarcinoma.异质性胰腺导管腺癌中的代谢可塑性
Biochim Biophys Acta. 2016 Dec;1866(2):177-188. doi: 10.1016/j.bbcan.2016.09.001. Epub 2016 Sep 4.
5
ETS-Transcription Factor ETV1 Regulates Stromal Expansion and Metastasis in Pancreatic Cancer.ETS转录因子ETV1调控胰腺癌的基质扩张和转移。
Gastroenterology. 2016 Sep;151(3):540-553.e14. doi: 10.1053/j.gastro.2016.06.005. Epub 2016 Jun 16.
6
MYB Promotes Desmoplasia in Pancreatic Cancer through Direct Transcriptional Up-regulation and Cooperative Action of Sonic Hedgehog and Adrenomedullin.MYB通过直接转录上调以及音猬因子和肾上腺髓质素的协同作用促进胰腺癌的促结缔组织增生性反应。
J Biol Chem. 2016 Jul 29;291(31):16263-70. doi: 10.1074/jbc.M116.732651. Epub 2016 May 31.
7
Genotype tunes pancreatic ductal adenocarcinoma tissue tension to induce matricellular fibrosis and tumor progression.基因型调节胰腺导管腺癌组织张力以诱导基质细胞纤维化和肿瘤进展。
Nat Med. 2016 May;22(5):497-505. doi: 10.1038/nm.4082. Epub 2016 Apr 18.
8
Lysyl oxidase family activity promotes resistance of pancreatic ductal adenocarcinoma to chemotherapy by limiting the intratumoral anticancer drug distribution.赖氨酰氧化酶家族活性通过限制肿瘤内抗癌药物分布促进胰腺导管腺癌对化疗的耐药性。
Oncotarget. 2016 May 31;7(22):32100-12. doi: 10.18632/oncotarget.8527.
9
Genetics and biology of pancreatic ductal adenocarcinoma.胰腺导管腺癌的遗传学与生物学
Genes Dev. 2016 Feb 15;30(4):355-85. doi: 10.1101/gad.275776.115.
10
SPARC-Independent Delivery of Nab-Paclitaxel without Depleting Tumor Stroma in Patient-Derived Pancreatic Cancer Xenografts.在患者来源的胰腺癌异种移植模型中，无基质金属蛋白酶组织抑制因子（SPARC）依赖的纳米白蛋白结合型紫杉醇递送，且不消耗肿瘤基质。
Mol Cancer Ther. 2016 Apr;15(4):680-8. doi: 10.1158/1535-7163.MCT-15-0764. Epub 2016 Feb 1.
Zotero 插件