Honselmann Kim Christin, Pross Moritz, Jung Carlo Maria Felix, Wellner Ulrich Friedrich, Deichmann Steffen, Keck Tobias, Bausch Dirk
Department of General-, Visceral-, Thoracic and Vascular Surgery, University Medical Center Schleswig-Holstein, Campus Luebeck. Luebeck, Germany.
JOP. 2015 Jan 31;16(1):25-32. doi: 10.6092/1590-8577/2894.
Pancreatic ductal adenocarcinoma (PDAC) is the fourth most common cause of death from cancer. Its 5-year survival rate is less than 5%. This poor prognosis is mostly due to the cancer's early invasion and metastasis formation, leading to an initial diagnosis at an advanced incurable stage in the majority of patients. The only potentially curative treatment is radical surgical resection. The effect of current chemotherapeutics or radiotherapy is limited. Novel therapeutic strategies are therefore much needed. One of the hallmarks of PDAC is its abundant desmoplastic (stromal) reaction. The Hedgehog (Hh) signaling pathway is critical for embryologic development of the pancreas. Aberrant Hh signaling promotes pancreatic carcinogenesis, the maintenance of the tumor microenvironment and stromal growth. The canonical Hh-pathway in the tumor stroma has been targeted widely but has not yet lead to hopeful clinical results. Targeting both the tumor and its surrounding stroma through Hh pathway inhibition by also targeting non-canonical pathways as apparent in the tumor cell may therefore be a novel treatment strategy for PDAC.
胰腺导管腺癌（PDAC）是癌症致死的第四大常见病因。其5年生存率低于5%。这种预后不良主要归因于癌症的早期侵袭和转移形成，导致大多数患者在晚期无法治愈阶段才得到初步诊断。唯一可能治愈的治疗方法是根治性手术切除。目前的化疗或放疗效果有限。因此，非常需要新的治疗策略。PDAC的一个标志是其丰富的促结缔组织增生（基质）反应。刺猬信号通路（Hh）对胰腺的胚胎发育至关重要。异常的Hh信号促进胰腺癌发生、肿瘤微环境的维持和基质生长。肿瘤基质中的经典Hh通路已被广泛靶向，但尚未带来理想的临床结果。因此，通过抑制Hh通路同时靶向肿瘤及其周围基质，同时也靶向肿瘤细胞中明显存在的非经典通路，可能是PDAC的一种新治疗策略。
