Stromal biology and therapy in pancreatic cancer
Stromal biology and therapy in pancreatic cancer
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DOI：
10.1136/gut.2010.226092
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发表时间：
2011-06-01
期刊：
影响因子：
24.5
通讯作者：
Tuveson, David A.
中科院分区：
文献类型：
--
作者：
Neesse, Albrecht;Michl, Patrick;Tuveson, David A.
胰腺导管腺癌（PDA）是一种几乎一致致死的疾病。对这种毁灭性预后的一种解释是许多化疗的失败，包括目前的标准治疗吉西他滨。虽然我们的知识的分子事件的基础上的多步骤癌发生在PDA稳步增加，翻译成更有效的治疗方法一直效率低下，在过去的几十年。最近在PDA的精确小鼠模型中提供了这种对全身治疗的先天抗性的证据，该模型证明了由于血管系统缺陷，化疗药物难以递送至PDA组织。这种血管缺陷与致密基质的存在相关，致密基质是PDA肿瘤的突出组织学标志。间质细胞的治疗靶向减少了胰腺肿瘤的间质，导致肿瘤内灌注和吉西他滨的治疗递送增加。因此，PDA肿瘤微环境中包含的基质细胞代表了肿瘤细胞的额外成分，应在临床前模型和早期临床试验中对最佳治疗开发进行严格评估。
Pancreatic ductal adenocarcinoma (PDA) is an almost uniformly lethal disease. One explanation for the devastating prognosis is the failure of many chemotherapies, including the current standard of care therapy gemcitabine. Although our knowledge of the molecular events underlying multistep carcinogenesis in PDA has steadily increased, translation into more effective therapeutic approaches has been inefficient over the last several decades. Evidence for this innate resistance to systemic therapies was recently provided in an accurate mouse model of PDA by the demonstration that chemotherapies are poorly delivered to PDA tissues because of a deficient vasculature. This vascular deficiency correlated with the presence of a dense stromal matrix that is a prominent histological hallmark of PDA tumours. Therapeutic targeting of stromal cells decreased the stroma from pancreatic tumours, resulting in increased intratumoral perfusion and therapeutic delivery of gemcitabine. Stromal cells contained within the PDA tumour microenvironment therefore represent an additional constituent to neoplastic cells that should be critically evaluated for optimal therapeutic development in preclinical models and early clinical trials.