Muñoz Amanda R, Chakravarthy Divya, Gong Jingjing, Halff Glenn A, Ghosh Rita, Kumar Addanki P
Department of Urology, The University of Texas Health Science Center, San Antonio, TX.
Department of Surgery, The University of Texas Health Science Center, San Antonio, TX.
Curr Pharmacol Rep. 2017 Dec;3(6):396-408. doi: 10.1007/s40495-017-0112-3. Epub 2017 Oct 11.
The 5-year survival rate of patients with pancreatic cancer (PanCA) has remained stagnant. Unfortunately, the incidence is almost equal to mortality rates. These facts underscore the importance of concerted efforts to understand the pathology of this disease. Deregulation of multiple signaling pathways involved in a wide variety of cellular processes including proliferation, apoptosis, invasion, and metastasis contribute not only to cancer development but also to therapeutic resistance. The purpose of this review is to summarize current understanding of etiological factors including emerging evidence on the role of infectious agents, factors associated with therapeutic resistance and therapeutic options.
The unique aspect of PanCA is "desmoplasia", a process that involves proliferation of stromal fibroblasts and collagen deposition in and around the filtrating cancer. Recent studies have identified pancreatic stellate cells (PSCs) as a potential source of such desmoplasia. Biphasic interactions between PSCs and cancer cells, endothelial cells, and/or myeloid derived suppressor cells in the tumor microenvironment contribute to pancreatic carcinogenesis.
We summarize limitations of current therapeutic approaches and potential strategies to overcome these limitations using natural products including botanicals as adjuvant/neo-adjuvant for effective management of PanCA.
胰腺癌患者的5年生存率一直停滞不前。不幸的是,发病率几乎与死亡率相当。这些事实凸显了共同努力了解该疾病病理的重要性。多种信号通路失调涉及包括增殖、凋亡、侵袭和转移在内的多种细胞过程,这不仅促进癌症发展,还导致治疗耐药性。本综述的目的是总结对病因学因素的当前认识,包括关于感染因子作用的新证据、与治疗耐药性相关的因素以及治疗选择。
胰腺癌的独特之处在于“促纤维增生”,这一过程涉及基质成纤维细胞增殖以及浸润性癌内和周围的胶原沉积。最近的研究已将胰腺星状细胞确定为这种促纤维增生的潜在来源。肿瘤微环境中胰腺星状细胞与癌细胞、内皮细胞和/或髓源性抑制细胞之间的双相相互作用有助于胰腺癌的发生。
我们总结了当前治疗方法的局限性以及使用包括植物药在内的天然产物作为辅助/新辅助治疗以有效管理胰腺癌的潜在策略,以克服这些局限性。