Pancreatic Adenocarcinoma and Epidermal Growth Factor Receptor

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Figure: (1) Oblique coronal CT abdomen. There is a hypodense heterogeneous mass in the head of the pancreas consistant with pancreatic adenocarcinoma.(red arrow) It is causing obstruction of the common bile duct (white arrowhead). (2) The extracellular domain of EGFR bound to EGF. (3) Domain structure of EGFR. SOURCE of (2) and (3) Wikipedia.

Pancreatic adenocarcinoma is the fifth most common human cancer. It usually presents as a focal mass (95%). It is most often in the pancreatic head (66%). With CT pancreatic adenocarcinoma is usually a small low-density mass. There is often invasion of local structures. There may be obstruction of the bile and pancreatic ducts and encasement of vessels. Distant metastases are most common in the liver and local nodes. Prognosis has been poor as the cancer is usually advanced at the time of diagnosis. New therapies based on biological response modifiers are starting to appear.Epidermal growth factor receptor (EGFR) is the receptor for epidermal growth factor (EGF). It is a member of the Erb B family of tyrosine kinase receptors. Kinases are protein switches that activate other proteins by adding a phosphate group to them via a process called phosphorylation. Mutations activating EGFR expression can result in cancer. EGFR is a transmembrane cell surface receptor. When inactive it is an isolated monomer. It is activated by binding specific ligands, including epidermal growth factor, transformation growth factor α , among others. EGFR then pairs with another EGFR or another Erb B receptor to form an active dimer. Dimerization stimulates tyrosine kinase domain activity of EGFR which starts a signal transduction, involving the mitogen activated protein kinase (MAPK) cascade, leading to DNA synthesis and cell proliferation. Dimerization can also result in autophosphorylation of tyrosine residues in the cytoplasmic domain of EGFR and activation of other proteins different from those signaled by the tyrosine kinase domain of EGFR. These proteins may be involved in such cellular functions as migration, adhesion, and proliferation. Mutations involving EGFR can lead to its constant activation resulting in uncontrolled cell division. EGFR was the first cell surface receptor linked to cancer. (Cohen et al 1976). The identification of EGFR as an oncogene has led to the development of monoclonal antibody therapy directed against EGFR, including gefitinib and erlotinib for lung cancer and pancreatic cancer, cetuximab for colon cancer, and trastuzumab for breast cancer.

Sources:

OMIM 131550

Lemoine NR, Hughes CM, Barton CM, Poulsom R, Jeffery RE, Kloppel G, Hall PA, Gullick WJ.The epidermal growth factor receptor in human pancreatic cancer. Molecular Pathology Laboratory, Hammersmith Hospital, London, U.K. J Pathol. 1992 Jan;166(1):7-12

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