C225讲课概要1.ppt

EGFR overviewEGFR 回顾 Role of Epidermal Growth FactorReceptor (EGFR) in human cancerEGFR在人类癌症中的作用 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 signaling The EGFR is activated by growth factors (e.g. epidermal growth factor [EGF] and transforming growth factor-? [TGF-?]). EGFR-activation leads to the building of either receptor homo- or hetero-dimers. Receptor dimerization initiates an intracellular signaling cascade, gene activation and the stimulation of cell cycle progression. EGFR expression inselected human tumors EGFR expression –clinical significance The importance of EGFR in mCRC 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: 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 The importance of EGFR as a target “Evidence for a role for the EGFR in the inhibition and pathogenesis of various cancers has led to the rational design and development of agents that selectively target this receptor.” EGFR-targeting approaches There are various mechanisms by which the EGFR can be blocked. EGFR inhibition via monoclonal antibodies blocking ligand binding EGFR-targeting antibodies are designed