The role of protein kinase C-alpha (PKC-alpha) in malignancies of the gastrointestinal tract.
Drugs specifically designed to block cellular signalling proteins are currently evaluated as a new way to treat gastrointestinal tumours. One such "new targeted agent" is aprinocarsen, an antisense oligonucleotide that specifically blocks the mRNA of protein kinase C-alpha (PKC-alpha). Blocking PKC-alpha, an important cellular signalling molecule associated with tumour growth, is anticipated to result in tumour cell arrest and achieve clinical benefits. However, it is not known which patients may benefit most from a specific inhibition of PKC-alpha. Past experience with other novel targeted agents suggests that expression of the target molecule is an important factor for the success of such a specific therapy. Therefore, reviewing the specific role of PKC-alpha in various gastrointestinal tumours may contribute to focus the clinical development of selective or specific PKC-alpha inhibitors, such as aprinocarsen, on those patients with a distinctive PKC-alpha expression pattern.
Lahn
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M
Divison of Oncology Product Development, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285, USA. mkahn@lilly.com
Paterson
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BM
Sundell
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Ma
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D004791:Enzyme Inhibitors / Q000627:therapeutic use; D005770:Gastrointestinal Neoplasms / Q000188:drug therapy / Q000201:enzymology*; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000502:physiology; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000502:physiology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology*; D051571:Protein Kinase C-alpha
D004791:Enzyme Inhibitors; D007527:Isoenzymes; D009363:Neoplasm Proteins; C496628:PRKCA protein, human; D011493:Protein Kinase C; D051571:Protein Kinase C-alpha