Recombinant toxin DAB389EGF is cytotoxic to human pancreatic cancer cells.
Few malignancies have frustrated the persistent efforts of the oncologist like pancreatic cancer. Pancreatic cancer is usually unresectable at the time of diagnosis because of metastasis or local extension. Despite the aggressive nature of this deadly disease, systemic treatment options are limited. Even the recent introduction of the deoxycytidine analogue gemcitabine does not extend median survival of responders beyond a year. Clearly, alternative, more effective regimens are needed for treating pancreatic carcinoma. In pancreatic cancer, there is overexpression of growth factors and growth factor receptors, including epidermal growth factor receptor (EGFR). Targeted toxins consist of a targeting polypeptide covalently linked to a peptide toxin. DAB(389)EGF is a fusion protein composed of the catalytic and translocation domains of diphtheria toxin fused via a His-Ala linker to human epidermal growth factor (EGF). The authors have previously shown that DAB(389)EGF is selectively toxic to EGFR-overexpressing cells, including human brain tumour and lung carcinoma cell lines. Pancreatic adenocarcinoma should be responsive to this fusion protein based on its EGFR overexpression. However, the cytotoxic effect of DAB(389)EGF on human pancreatic carcinoma cell lines has yet to be explored. The authors describe preliminary data showing the potent cytotoxicity of DAB(389)EGF to human pancreatic carcinoma cell lines. Because of the nonspecific toxicity to liver and kidney (which possess EGFR) of systemic administration, they also propose a potential novel drug delivery system for direct toxin implantation into pancreatic tumours using endoscopic ultrasound guided fine-needle injection (EUS-FNI). Hopefully, the use of these targeted therapeutic approaches in combination with other modalities may further extend survival and quality of life in patients with pancreatic adenocarcinoma.
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004167:Diphtheria Toxin / Q000235:genetics; D018773:Genes, erbB-1 / Q000235:genetics; D006801:Humans; D007267:Injections; D010179:Pancreas; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000494:pharmacology*
D000970:Antineoplastic Agents; C487796:DAB389EGF protein, human; D004167:Diphtheria Toxin; D011993:Recombinant Fusion Proteins