Drug Targets for Pancreatic Cancer

Drug Targets for Pancreatic Cancer

Drug Targets EGFR for Pancreatic Cancer with Approved Drugs

Drug targets Cancer drugs Company
EGFR Erlotinib Genentech and OSI Pharmaceuticals and elsewhere by Roche

In the normal pancreas, EGFR expression is limited to ductal cells and the islets of Langerhans. Similar to a number of other malignancies, EGFR has been shown to be overexpressed in pancreatic cancers. EGFR overexpression with resultant increase in EGFR signaling may be associated with metastatic potential and decreased survival in patients with pancreatic cancer. Preclinical studies show that EGFR-mediated signaling is involved in tumorigenesis of pancreatic cancer. Erlotinib is a small molecule tyrosine kinase inhibitor (TKI) with specificity for EGFR. Based on the findings of preclinical studies and early phase clinical trials, the National Cancer Institute of Canada Clinical Trials Group (NCIC-CTG) conducted a phase III study (PA.3) comparing single-agent gemcitabine to gemcitabine in combination with erlotinib as first-line therapy for advanced pancreatic cancer. The PA.3 study became the first phase III randomized study to demonstrate a significant survival benefit with combination therapy as well as with a targeted agent in advanced pancreatic cancer. (Kelley RK, et al. Erlotinib in the treatment of advanced pancreatic cancer. Biologics : Targets & Therapy. 2008;2(1):83-95.)

Drug Targets mTOR for Pancreatic Cancer with Approved Drugs

Drug targets Cancer drugs Company
mTOR Everolimus Novartis

Everolimus has recently shown promising antitumor activity in two phase 2 studies involving patients with pancreatic neuroendocrine tumors. Everolimus inhibits mammalian target of rapamycin (mTOR), a serine–threonine kinase that stimulates cell growth, proliferation, and angiogenesis. Autocrine activation of the mTOR signaling pathway, mediated through insulin-like growth factor 1, has been implicated in the proliferation of pancreatic neuroendocrine tumor cells. Consistent with this observation is the finding that inhibition of mTOR has a significant antiproliferative effect on pancreatic neuroendocrine tumor cell lines. (Yao J C, et al. Everolimus for advanced pancreatic neuroendocrine tumors[J]. New England Journal of Medicine, 2011, 364(6): 514-523.)

Drug Targets on Angiogenesis for Pancreatic Cancer with Approved Drugs

Drug target Cancer drugs Company
VEGFR-2, VEGFR-3, PDGFRα, PDGFRβ, c-kit Everolimus Pfizer

Vascular endothelial growth factor (VEGF) is a key driver of angiogenesis in pancreatic neuroendocrine tumors. Tissue from malignant pancreatic endocrine tumors also shows widespread expression of platelet-derived growth factor receptors (PDGFRs) α and β, stem-cell factor receptor (c-kit), and VEGF receptor (VEGFR)-2 and VEGFR-3. Sunitinib malate (Sutent, Pfizer) inhibits these kinases and delays tumor growth in a RIP1-Tag2 transgenic mouse model of pancreatic islet-cell tumors by reducing endothelial-cell density and pericyte coverage of tumor vessels. In phase 1 and 2 trials, sunitinib showed antitumor activity in patients with pancreatic neuroendocrine tumors. (Raymond E, et al. Sunitinib malate for the treatment of pancreatic neuroendocrine tumors[J]. New England Journal of Medicine, 2011, 364(6): 501-513.)

Drug targets for Pancreatic cancer: Related Information