EGFR和昔妥西单抗总论.pptVIP

EGFR Overview Role of Epidermal Growth FactorReceptor (EGFR) in Human Cancer EGFR critically regulates tumor cell cycle progression, repair, and survival, and is involved in tumor metastasis Binding of specific ligands to EGFR (eg, EGF, TGF-a) activates the receptor and triggers signal transduction cascades that affect cell proliferation Many human cancers express EGFR on the cell surface Inhibition of EGFR on tumor cells may inhibit the growth or progression of EGFR-expressing tumors EGFR Signal Transduction EGFR Expression in Selected Human Tumors EGFR Expression: Clinical Significance Use of Immunohistochemistry (IHC) to Detect EGFR Expression in Tumors IHC detects expression of EGFR protein on surface of tumor cells, with direct visualization of the target Reagents and equipment are commonly available IHC is widely used in clinical studies Standardized methods are being developed Rationale for EGFR Blockade EGFR is expressed in a significant % of all solid tumors EGFR has multiple mechanisms of action including: Promoting growth of tumor cells Aiding in repair/survival for tumor cells damaged by CT/RT Playing an important role in angiogenesis Playing a critical role in invasion and metastases EGFR expression is an indicator of poor prognosis, decreased survival, and increased metastases Tumors that express EGFR have a high level of unmet medical need EGFR-targeting Approaches EGFR Inhibition Via Monoclonal Antibodies Blocking Ligand Binding EGFR Overview - Conclusions EGFR may play a critical role in regulating tumor cell growth, repair and survival, angiogenesis, invasion, and metastasis EGFR is expressed in a significant percentage of human tumors and is correlated with poor prognosis, decreased survival, and/or increased metastasis Agents designed to block EGFR activity are postulated to: Inhibit phosphorylation and signal transduction Result in multiple antitumor mechanisms Enhance chemotherapy and radiotherapy antitumor effects Ongoing trials are e