MECHANISM OF ACTION : Inhibiting binding of ligands (specifically epidermal growth factor) to EGFR and inhibiting EGFR-mediated signal transduction, resulting in inhibition of cell proliferation; Reduction in tumor-associated angiogenesis; Induction of apoptosis and increased effects for radiation and ...
monoclonal antibodies (mAbs) have been widely used to treat various diseases, such as cancers, immune disorders, and infections2,3,4. However, the emergence of primary (de novo) or secondary (acquired) resistance with different underlying
To probe the mechanism of action behind the combination treatment, we first evaluated their impacts on EGFR signaling in 20ins cell lines. Immunoblot analysis was performed on Ba/F3 cells expressing EGFR insASV, insSVD and insNPH. Combining JMT101 with afatinib or osimertinib strongly inhibited EG...
Intimately connected to their mechanism of action, the benefit of anti-EGFR mAbs is bypassed by gain-of-function mutations in KRAS, a signalling molecule downstream of EGFR (Amado et al, 2008; Karapetis et al, 2008; Bokemeyer et al, 2009; Van Cutsem et al, 2009). Indeed, in subjects...
Sym004, currently in phase II trials, is a novel mixture of two anti-EGFR monoclonal antibodies binding non-overlapping epitopes in the extracellular domain III of EGFR. The primary mechanism of action of Sym004 is thought to be EGFR cross-linking, internalization and degradation of the EGFR ...
PIK3CA mutations in colorectal cancer are associated with clinical resistance to EGFR-targeted monoclonal antibodies. Cancer Res. 2009;69:1851–7. CrossRef Zhao L, Vogt PK. Helical domain and kinase domain mutations in p110alpha of phosphatidylinositol 3-kinase induce gain of function by different...
To verify the in vivo mechanism of action, Western analysis and immunohistochemistry were performed on tumor samples at the end of the 10-treatment course. For Western analysis, whole cell protein extracts were obtained with radio-immunoprecipitation assay buffer following standard protocols (Santa Cruz...
Anti-epidermal growth factor receptor (EGFR) antibodies (anti-EGFR-Ab) are effective in a subgroup of patients (pts) with metastatic colorectal cancer (CRC). Activating KRAS or NRAS mutations in codons 12, 13, 59, 61, 117, and 146 have been associated with primary resistance in randomized ...
2.3. Combined Use of Anti-EGFR-Tyrosine Kinase Inhibitors (TKI) and Anti-EGFR-Antibody Cetuximab in Ovarian Cancer Cells The different mode of action of monoclonal antibodies and TKIs might suggest that the combined use of both substances might increase antitumoural activity. Therefore, we ...
To date, only two antibodies against the murine EGFR (mEGFR) are known, the 7A7 [24] and another antibody produced by ImClone [25]. Previous studies show that the so-called 7A7 antibody (7A7-Ab) recognizes the extracellular domain of the mEGFR on healthy cells and tumor cells. In ad...