Provider: Ingenta Connect Database: Ingenta Connect Content: application/x-research-info-systems TY - ABST AU - Johnston, James B. AU - Navaratnam, Sri AU - Pitz, Marshall W. AU - Maniate, Jerry M. AU - Wiechec, Emilia AU - Baust, Heinrich AU - Gingerich, Joel AU - Skliris, Georgios P. AU - Murphy, Leigh C. AU - Los, Marek TI - Targeting the EGFR Pathway for Cancer Therapy JO - Current Medicinal Chemistry PY - 2006-12-01T00:00:00/// VL - 13 IS - 29 SP - 3483 EP - 3492 KW - gefitinib KW - EGFR KW - erlotinib KW - cancer therapy KW - cetuximab KW - lapatinib KW - trastuzumab N2 - Clinical studies have shown that HER-2/Neu is over-expressed in up to one-third of patients with a variety of cancers, including B-cell acute lymphoblastic leukemia (B-ALL), breast cancer and lung cancer, and that these patients are frequently resistant to conventional chemo-therapies. Additionally, in most patients with multiple myeloma, the malignant cells over-express a number of epidermal growth factor receptors (EGFR)s and their ligands, HB-EGF and amphiregulin, thus this growth-factor family may be an important aspect in the patho-biology of this disease. These and other, related findings have provided the rationale for the targeting of the components of the EGFR signaling pathways for cancer therapy. Below we discuss various aspects of EGFR-targeted therapies mainly in hematologic malignancies, lung cancer and breast cancer. Beside novel therapeutic approaches, we also discuss specific side effects associated with the therapeutic inhibition of components of the EGFR-pathways. Alongside small inhibitors, such as Lapatinib (Tykerb, GW572016), Gefitinib (Iressa, ZD1839), and Erlotinib (Tarceva, OSI-774), a significant part of the review is also dedicated to therapeutic antibodies (e.g.: Trastuzumab / Herceptin, Pertuzumab / Omnitarg / rhuMab-2C4, Cetuximab / Erbitux / IMC-C225, Panitumumab / Abenix / ABX-EGF, and also ZD6474). In addition, we summarize, both current therapy development driven by antibody-based targeting of the EGFR-dependent signaling pathways, and furthermore, we provide a background on the history and the development of therapeutic antibodies. UR - https://www.ingentaconnect.com/content/ben/cmc/2006/00000013/00000029/art00001 M3 - doi:10.2174/092986706779026174 UR - https://doi.org/10.2174/092986706779026174 ER -