Pancreatic cancer: from molecular pathogenesis to targeted therapy

• Published in: Cancer and metastasis reviews Vol. 27; no. 3; pp. 495 - 522
• Main Authors: Strimpakos, Alexios, Saif, Muhammad W., Syrigos, Kostas N.
• Format: Journal Article
• Language: English
• Published: Boston Springer US 01.09.2008; Springer; Springer Nature B.V
• Subjects: Animals; Antineoplastic Agents - therapeutic use; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; c-Met protein; Cancer Research; Cancer therapies; Chemotherapy; Clinical Trials as Topic; Cytotoxicity; Drug Delivery Systems - methods; Gastroenterology. Liver. Pancreas. Abdomen; Gemcitabine; Gene therapy; Histone deacetylase; Humans; Immunotherapy; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Malignancy; Medical sciences; Monoclonal antibodies; NF-κB protein; Non-Thematic Review; Oncology; Pancreatic cancer; Pancreatic Neoplasms - physiopathology; Pancreatic Neoplasms - therapy; Proteasomes; Protein-tyrosine kinase; TOR protein; Tumors; Targeted therapies; Pancreatic adenocarcinoma; Monoclonal antibodies; Novel agents; Molecular pathophysiology; Tyrosine kinase inhibitors; Pathophysiology; Enzyme; Antibody; Pathogenesis; Targeted therapy; Transferases; Malignant tumor; Tyrosine kinase inhibitors .Novel agents .Targeted therapies; Cancerology; Treatment; Pancreas cancer; Digestive diseases; Inhibitor; Molecular pathophysiology· Pancreatic adenocarcinoma .Monoclonal antibodies; Protein-tyrosine kinase; Pancreas adenocarcinoma; Cancer; Pancreatic disease
• ISSN: 0167-7659; 1573-7233
• DOI: 10.1007/s10555-008-9134-y

Pancreatic cancer is a deadly malignancy with still high mortality and poor survival despite the significant advances in understanding, diagnosis, and access to conventional and novel treatments. Though cytotoxic chemotherapy based on the purine analogue gemcitabine remains the standard approach in adjuvant and palliative setting the need for novel agents aiming at the main pathophysiological abnormalities and molecular pathways involved remains soaring. So far, evidence of clinical benefit, though small, exists only from the addition of the targeted agent erlotinib on the standard gemcitabine chemotherapy. Apart from the popular monoclonal antibodies and small molecules tyrosine kinase inhibitors, other novel compounds being tested in preclinical and clinical studies target mTOR, NF-κB, proteasome and histone deacetylase. These new drugs along with gene therapy and immunotherapy, which are also under clinical evaluation, may alter the unfavorable natural course of this disease. In this review we present the main pathophysiological alterations met in pancreatic cancer and the results of the florid preclinical and clinical research with regards to the targeted therapy associated to these abnormalities.