This paper focuses on lapatinib, a small molecule inhibitor of tyrosine kinases of the EGFR and HER2. The r Approved by lapatinib as first-line NVP-ADW742 ADW742 treatment of patients with metastatic breast cancer, with current data, undefined. Evaluation of lapatinib pharmacology, efficacy and reps Opportunity and a diaphragm U lapatinib available data makes It resembled ourselves, St To identify strengths and challenges of lapatinib and suggest its R Potential in the treatment of primary Ren metastatic breast cancer. The type I ErbB family of receptor tyrosine kinases consists of four transmembrane receptors: ErbB1, ErbB2, ErbB3 and ErbB4. ErbB2 no exogenous ligands. ErbB3 Kinaseaktivit no t.
The binding of the ligands of these ErbB receptors leads to the formation of heterodimers or homodimers, which induces autophosphorylation PF-04217903 of specific residues at the conserved tyrosine kinase catalytic domain NEN of ErbB receptors. Is autophosphorylation of tyrosine kinase binding sites for Src homology 2 and phosphotyrosine-binding Dom bound proteins With ErbB intracellular activation link Rer signaling pathways downstream of the path of cell proliferation and the streets to survive e of the cell. ErbB2, while w They no exogenous ligand is the preferred partner for heterodimerization with ErbB1, ErbB3 and ErbB4, as it comes with a strong mitogenic signal growth and survival effects. This is the r The key receptor in the ErbB tumor cell growth and survival, which make them attractive therapeutic targets. Monoclonal Body such as cetuximab and trastuzumab, on the extracellular Ren Dom NEN of ErbB2 and ErbB1.
Small molecules intracellularly Ren tyrosine kinase inhibitors also go Ren ErbB1 erlotinib, gefitinib and lapatinib, which inhibits HER2 tyrosine kinase. Targeting the EGFR in breast cancer showed no significant clinical activity T. In contrast, the efficacy of inhibitors of the HER2 receptor has provided a significant improvement in the outlook for patients with HER2-positive disease are available. Lapatinib Lapatinib is an orally active, small molecule that inhibits the F ErbB1 and ErbB2 is reversible. The simultaneous inhibition of ErbB1 and ErbB2-expressing tumors overexpressed blocked the activation of signaling cascades in the MAPK and PI3K signaling pathways which show growth arrest and / or apoptosis, as shown in cell lines and xenograft models.
1, 2 Pr Clinical models what can be cytostatic or cytotoxic, depending on cell type. HN HN NN Cl OOSOOF Figure 1 Chemical structure of lapatinib. Cancer Management and Research 2010:2 15 Dovepress lapatinib primarily MBC you submit your manuscript | dovepress.com Dovepress efficacy of lapatinib is dependent ngig of the biological profile of a tumor inh pensions. Tumor dependence Dependence of EGFR and / or HER2-cell proliferation and survival is the ideal destination for lapatinib. Ltigungsstrategien tumors with innate or Ratings Not EGFR and / or HER2 are developed h Depends on the Best Civil Engineering, Civil or reduced susceptibility to therapy. Although lapatinib is aimed at both EGFR and HER2, its effect on HER2 appear to be critical to its effectiveness. Pharmacology and pharmacokinetics of lapatinib has been developed as an oral agent and has no equivalent intravenous See It is recommended as a 250-mg tablet and a single dose of currently at least 1 hour before or after a meal.3 After an oral dose, focused measurable lapatinib