INSERM UMR 911-CR02, Faculty of Medicine, 27 BL Jean Moulin, Marseille 13005, France.
Expert Opin Ther Targets. 2010 May;14(5):541-52. doi: 10.1517/14728221003769895.
With some 220,000 new cases/year in the world, pancreatic adenocarcinoma is the fourth highest cause of death by cancers. Among newly diagnosed patients about 210,000 will die within 9 months following diagnosis. Therefore, effective adjuncts to current treatment strategies are necessary. Because embryological signaling pathways are upregulated in pancreatic adenocarcinoma, they represent potential targets for future therapies.
Our aim is to present the Notch pathway, and to describe its involvement in pancreatic pathophysiology/carcinogenesis. This pathway appeared as a prime target for pancreatic cancer therapy. In the light of the crosstalk of Notch with other survival/embryologic pathways, drugs affecting more than one pathway may have to be combined.
Drugs against gamma-secretases could thus serve in cancer treatment and can be combined with drugs targeting survival pathways interplaying with Notch such as Hedgehog.
Downregulation of Notch contributes to the inhibition and apoptosis of pancreatic cancer cells whereas Hedgehog inhibition will allow for enhanced delivery of drugs to the tumor. Both pathway inhibitors appear to have synergistic effects for future therapeutics for pancreatic adenocarcinoma, once safety issues of compounds are overcome.
全世界每年约有 22 万例新发病例，胰腺癌是癌症死亡的第四大主要原因。在新诊断的患者中，约有 21 万人在诊断后 9 个月内死亡。因此，有必要寻找有效的辅助治疗策略。由于胚胎信号通路在胰腺腺癌中上调，它们代表了未来治疗的潜在靶点。
我们的目的是介绍 Notch 通路，并描述其在胰腺生理/癌变中的作用。该通路似乎是胰腺癌治疗的主要靶点。鉴于 Notch 与其他生存/胚胎信号通路的相互作用，可能需要联合使用作用于多个通路的药物。
针对 γ-分泌酶的药物可用于癌症治疗，并可与与 Notch 相互作用的生存通路靶向药物（如 Hedgehog）联合使用。
Notch 通路的下调可抑制和诱导胰腺癌细胞凋亡，而 Hedgehog 通路的抑制可增强药物向肿瘤的传递。一旦克服了化合物的安全性问题，两种通路抑制剂似乎都对未来治疗胰腺腺癌具有协同作用。
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