Topic Highlight
Copyright ©2014 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Mar 7, 2014; 20(9): 2335-2342
Published online Mar 7, 2014. doi: 10.3748/wjg.v20.i9.2335
Hedgehog signaling pathway as a new therapeutic target in pancreatic cancer
Hideya Onishi, Mitsuo Katano
Hideya Onishi, Mitsuo Katano, Department of Cancer Therapy and Research, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan
Author contributions: Onishi H and Katano M analyzed the data; Onishi H wrote the paper.
Supported by The Japan Society for the Promotion of Science, Kakenhi Grant, No. 24390303
Correspondence to: Hideya Onishi, MD, PhD, Department of Cancer Therapy and Research, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan. ohnishi@surg1.med.kyushu-u.ac.jp
Telephone: +81-92-6426220 Fax: +81-92-6426221
Received: October 7, 2013
Revised: December 11, 2013
Accepted: January 8, 2014
Published online: March 7, 2014
Processing time: 150 Days and 4.6 Hours
Abstract

Pancreatic cancer is one of the most aggressive and difficult cancers to treat. Despite numerous research efforts, limited success has been achieved in the therapeutic management of patients with this disease. In the current review, we focus on one component of morphogenesis signaling, Hedgehog (Hh), with the aim of developing novel, effective therapies for the treatment of pancreatic cancer. Hh signaling contributes to the induction of a malignant phenotype in pancreatic cancer and is responsible for maintaining pancreatic cancer stem cells. In addition, we propose a novel concept linking Hh signaling and tumor hypoxic conditions, and discuss the effects of Hh inhibitors in clinical trials. The Hh signaling pathway may represent a potential therapeutic target for patients with refractory pancreatic cancer.

Keywords: Hedgehog signaling pathway; Pancreatic cancer; Cancer stem cells; Hypoxic condition; Therapeutic target

Core tip: Hedgehog (Hh) signaling is involved in the induction of malignant potential in pancreatic cancer, controlling processes of proliferation, invasiveness and tumorigenesis. This phenotypic change is closely associated with the nuclear factor kappa-light-chain-enhancer of activated B cells transcription factor, both in an autocrine and paracrine manner. Hh signaling is also capable of maintaining pancreatic cancer stem cells, and may be activated under conditions of tumor hypoxia. Thus, the Hh signaling pathway may represent a potential therapeutic target for patients with refractory pancreatic cancer and the use of Hh inhibitors will likely play an important role in future therapeutic strategies.