Science：增强抗癌作用的法宝

　　

生物通报道，最新一期的《Science》杂志刊发了一篇关于癌症化疗的研究，Inhibition of Hedgehog Signaling Enhances Delivery of Chemotherapy in a Mouse Model of Pancreatic Cancer。

 

这一研究主要揭示了Hedgehog信号在癌症药物传递过程中的重要作用， Hedgehog基因是一种分节极性基因，因突变的果蝇胚胎呈多毛团状，酷似受惊刺猬而得名。已知该基因编码一种高度保存的分泌型糖蛋白，对于调节果蝇胚胎发育中细胞定向分化有重要作用。随着对Hedgehog信号通路和肿瘤的深入研究，近年来已发现Hedgehog与多种肿瘤有关联。

 

早期杜克大学的赵忱研究员等在Nature上发表了Hedgehog对白血病癌症干细胞的作用，想了解更多请阅读专访赵忱的报道：专访Senior研究员赵忱用idea点亮生命http://www.ebiotrade.com/newsf/2009-5/2009519171454267.htm

 

在Science的这篇研究中，研究人员发现抑制Hedgehog信号通路能有效的增强化疗药物的传递，增强化疗的作用。本研究中以胰腺癌为研究模型，胰腺癌是目前人类最致命的癌症之一。目前对胰腺癌的治疗主要使用的是一种叫gemcitabin的药物，由于胰腺癌组织中血管稀少，gemcitabin无法传递到肿瘤组织中，因此不能发挥疗效，这种药物往往只能延长病人几个星期的寿命。

 

文字说明: 对于血管标记CD31的免疫组织化学染色法阐述了胰腺肿瘤细胞的结构。

 

资料来源: Kenneth P. Olive

 

 

为此，研究小组通过一种化合物抑制胰腺癌组织的Hedgehog信号，可有效的促进肿瘤内血管的增加，从而促进gemcitabin药物的传递，减缓肿瘤组织的生长。

 

这一成果为胰腺癌的治疗开辟了新的道路，也为其他种类癌症与Hedgehog信号的关系提供了借鉴意义。

(生物通 小茜)

生物通推荐原文检索：Inhibition of Hedgehog Signaling Enhances Delivery of Chemotherapy in a Mouse Model of Pancreatic Cancer

Kenneth P. Olive 1, Michael A. Jacobetz 1, Christian J. Davidson 2, Aarthi Gopinathan 3, Dominick McIntyre 1, Davina Honess 1, Basetti Madhu 1, Mae A. Goldgraben 1, Meredith E. Caldwell 1, David Allard 1, Kristopher K. Frese 1, Gina DeNicola 3, Christine Feig 1, Chelsea Combs 2, Stephen P. Winter 1, Heather Ireland 1, Stefanie Reichelt 1, William J. Howat 1, Alex Chang 4, Mousumi Dhara 4, Lifu Wang 5, Felix Rückert 6, Robert Grützmann 6, Christian Pilarsky 6, Kamel Izeradjene 7, Sunil R. Hingorani 7, Pearl Huang 8, Susan E. Davies 9, William Plunkett 10, Merrill Egorin 11, Ralph H. Hruban 4, Nigel Whitebread 12, Karen McGovern 12, Julian Adams 12, Christine Iacobuzio-Donahue 4, John Griffiths 1, David A. Tuveson 1*

1 Cancer Research UK, Cambridge Research Institute, The Li Ka Shing Centre, Robinson Way, Cambridge, CB2 ORE, UK.

2 Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, PA 19104, USA.

3 Cancer Research UK, Cambridge Research Institute, The Li Ka Shing Centre, Robinson Way, Cambridge, CB2 ORE, UK.; Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, PA 19104, USA.

4 Departments of Oncology and Pathology, The Sol Goldman Pancreatic Cancer Research Center, Sidney Cancer Center and Johns Hopkins University, Baltimore, MD 21287, USA.

5 Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, PA 19104, USA.; Department of Gastroenterology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China.

6 Department of Surgery, University Hospital Dresden, Fetscherstr. 74, 01307 Dresden, Germany.

7 Clinical Research and Public Health Sciences Division, Fred Hutchinson Cancer Research Center, and University of Washington, Seattle, WA 98109, USA.

8 Oncology Franchise, Merck and Co, North Wales, PA 19454, USA.

9 Department of Histopathology, Addenbrooke’s Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, CB2 2QQ, UK.

10 Univ. of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

11 Division of Hematology and Oncology, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA.

12 Infinity Pharmaceuticals Inc, Cambridge, MA 01239, USA.

【Abstract】

Pancreatic ductal adenocarcinoma (PDA) is among the most lethal human cancers, in part because it is insensitive to many chemotherapeutic drugs. Studying a mouse model of PDA that is refractory to the clinically used drug gemcitabine, we found that the tumors in this model were poorly perfused and poorly vascularized, properties that are shared with human PDA. We tested whether the delivery and efficacy of gemcitabine in the mice could be improved by coadministration of IPI-926, a drug that depletes tumor-associated stromal tissue by inhibiting the Hedgehog cellular signaling pathway. The combination therapy produced a transient increase in intratumoral vascular density and intratumoral concentration of gemcitabine, leading to transient stabilization of disease. Thus, inefficient drug delivery may be an important contributor to chemoresistance in pancreatic cancer.