Exploiting novel molecular targets in gastrointestinal cancers.
Novel molecular targets are being discovered as we learn more about the aberrant processes underlying various cancers. Efforts to translate this knowledge are starting to impact on the care of patients with gastrointestinal cancers. The epidermal growth factor receptor (EGFR) pathway and angiogenesis have been targeted successfully in colorectal cancer with cetuximab, panitunumab and bevacizumab. Similarly, EGFR-targeting with erlotinib yielded significant survival benefit in pancreatic cancer when combined with gemcitabine. The multi-targeting approach with sorafenib has made it the first agent to achieve significant survival benefit in hepatocellular carcinoma. Efforts to exploit the dysregulated Akt/mTOR pathway in GI cancer therapy are ongoing. These molecular targets can be disrupted by various approaches, including the use of monoclonal antibody to intercept extracellular ligands and disrupt receptor-ligand binding, and small molecule inhibitors that interrupt the activation of intracellular kinases.
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Wen W
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Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University School of Medicine, 1650 Orleans Street, CRB 1M88, Baltimore, MD 21231, United States.
Hidalgo
Manuel
M
D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use; D066246:ErbB Receptors / Q000187:drug effects / Q000502:physiology*; D005770:Gastrointestinal Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000503:physiopathology*; D006801:Humans; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000503:physiopathology; D011494:Protein Kinases / Q000187:drug effects / Q000502:physiology; D051057:Proto-Oncogene Proteins c-akt / Q000187:drug effects / Q000502:physiology; D058570:TOR Serine-Threonine Kinases
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D011494:Protein Kinases; C546842:MTOR protein, human; C512478:EGFR protein, human; D066246:ErbB Receptors; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases