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HER Family of Receptors as Treatment Targets in Pancreatic Cancer

  • Bhaumik B. Patel
  • Adhip P. N. Majumdar
Part of the M. D. Anderson Solid Tumor Oncology Series book series (MDA)

Genetic mutation is the hallmark of the development and progression of cancer. The most commonly found mutations in pancreatic cancer are K-ras, CDKN2A (9p), p53 (17q), and smad4 (18q) (1). Smoking, which has been linked to the K-ras mutation, is the most common mutation in pancreatic cancer, with >70% of all pancreatic cancers harboring codon 12 mutations (2). Pancreatic cancer, like colon adenocarcinoma, is believed to follow a genetic progression model with a progressively increasing number of mutations being acquired in a seemingly temporal sequence with morphologic progression from a normal ductal cell to low-grade PanIN to high-grade PanIN, leading to frank invasive adenocarcinoma (Fig. 36.1) (1). K-ras and CDKN2A appear to occur early in the process of carcinogenesis, leading to increased proliferation and shortening of telomere length. Shortened telomere length promotes genetic instability (1). P53 and BRCA2 mutations appear in the later stages, such as high-grade PanIN and invasive cancer (1). These mutations cause an impaired DNA damage checkpoint and promote development of aneuploid tumors (see Fig. 36.1).

K-ras mutation is an early and almost universal finding in pancreatic cancer. Besides activation of various downstream pathways, which include but are not limited to mitogen activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K), it also establishes autocrine HER family signaling in pancreatic cancer ( 1 ). This is evidenced by increased co-expression of various ligands and the signal transduction pathways induced by the member(s) of the HER family ( 1 ). Transforming growth factor- (TGF- ), EGF, and EGFR are over-expressed by 15-, 10-, and threefold compared with that in normal pancreatic tissue in the same tumor. This strongly suggests the existence of an autocrine activation loop involving EGFR in pancreatic cancer ( 3 ).

Keywords

Epidermal Growth Factor Receptor Clin Oncol Pancreatic Cancer Cell Human Pancreatic Cancer Advanced Pancreatic Cancer 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer Science + Business Media, LLC 2008

Authors and Affiliations

  • Bhaumik B. Patel
    • 1
  • Adhip P. N. Majumdar
    • 1
  1. 1.John D. Dingell VA Medical CenterDetroitUSA

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