Metabolic disorder, inflammation, and deregulated molecular pathways converging in pancreatic cancer development: Implications for new therapeutic strategies

• Motoo, Yoshiharu

• Shimasaki, Takeo

• Ishigaki, Yasuhito

• Nakajima, Hideo

• Kawakami, Kazuyuki

• Minamoto, Toshinari

Abstract

金沢大学医薬保健研究域医学系

Pancreatic cancer develops and progresses through complex, cumulative biological processes involving metabolic disorder, local inflammation, and deregulated molecular pathways. The resulting tumor aggressiveness hampers surgical intervention and renders pancreatic cancer resistant to standard chemotherapy and radiation therapy. Based on these pathologic properties, several therapeutic strategies are being developed to reverse refractory pancreatic cancer. Here, we outline molecular targeting therapies, which are primarily directed against growth factor receptor-type tyrosine kinases deregulated in tumors, but have failed to improve the survival of pancreatic cancer patients. Glycogen synthase kinase-3β (GSK3β) is a member of a serine/threonine protein kinase family that plays a critical role in various cellular pathways. GSK3β has also emerged as a mediator of pathological states, including glucose intolerance, inflammation, and various cancers (e.g., pancreatic cancer). We review recent studies that demonstrate the anti-tumor effects of GSK3β inhibition alone or in combination with chemotherapy and radiation. GSK3β inhibition may exert indirect anti-tumor actions in pancreatic cancer by modulating metabolic disorder and inflammation. © 2011 by the authors; licensee MDPI, Basel, Switzerland.

Journal

• Cancers

  Cancers 3 (1), 446-460, 2011-03-01

  MDPI Publishing

Keywords

• Glucose intolerance
• GSK3β
• Inflammation
• Oncogenic pathways
• Pancreatic cancer
• Therapeutic target

Details

• CRID: 1050845760880922496
• NII Article ID: 120003141569
• ISSN: 20726694
• Web Site: http://hdl.handle.net/2297/27790
• Text Lang: en
• Article Type: journal article
• Data Source:
  • IRDB
  • CiNii Articles