Stromal reengineering to treat pancreas cancer.
Stromal reengineering to treat pancreas cancer.
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DOI：
10.1093/carcin/bgu115
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发表时间：
2014-07
期刊：
影响因子：
4.7
通讯作者：
Ingunn M. Stromnes;Kathleen E. DelGiorno;P. Greenberg;S. Hingorani
中科院分区：
文献类型：
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作者：
Ingunn M. Stromnes;Kathleen E. DelGiorno;P. Greenberg;S. Hingorani
胰腺导管腺癌合并多种细胞和细胞外机制，以创建一个复杂的癌症器官，具有不寻常的转移倾向和耐药治疗。细胞自主性事件对于胰腺导管腺癌的发生和维持是必不可少的，但最近的研究表明，在促进疾病发病机制和抗性的稳健促纤维增生基质中存在关键的非细胞自主性过程。因此，非恶性细胞和相关因子是肿瘤生长、免疫抑制和侵袭的罪魁祸首。然而，即使人们越来越认识到非细胞自主对疾病进展的贡献，但基质成分可能发挥的相互冲突的作用也削弱了这种认识。对间质复杂性和复杂性的更深入理解部分得益于对高度忠实的胰腺导管腺癌基因工程小鼠模型的研究。从这些研究中获得的见解正在刺激旨在重新设计胰腺癌基质并使其允许靶向细胞自主事件或恢复免疫监视的药物的治疗方法的发展。在基质靶向的背景下整合常规和免疫治疗可能为这种可怕的疾病提供持久的临床影响的关键。
Pancreatic ductal adenocarcinoma co-opts multiple cellular and extracellular mechanisms to create a complex cancer organ with an unusual proclivity for metastasis and resistance to therapy. Cell-autonomous events are essential for the initiation and maintenance of pancreatic ductal adenocarcinoma, but recent studies have implicated critical non-cell autonomous processes within the robust desmoplastic stroma that promote disease pathogenesis and resistance. Thus, non-malignant cells and associated factors are culprits in tumor growth, immunosuppression and invasion. However, even this increasing awareness of non-cell autonomous contributions to disease progression is tempered by the conflicting roles stromal elements can play. A greater understanding of stromal complexity and complicity has been aided in part by studies in highly faithful genetically engineered mouse models of pancreatic ductal adenocarcinoma. Insights gleaned from such studies are spurring the development of therapies designed to reengineer the pancreas cancer stroma and render it permissive to agents targeting cell-autonomous events or to reinstate immunosurveillance. Integrating conventional and immunological treatments in the context of stromal targeting may provide the key to a durable clinical impact on this formidable disease.