Abstract
The epidermal growth factor receptor (EGFR) family contains four transmembrane tyrosine kinases (EGFR1/ErbB1, Her2/ErbB2, Her3/ErbB3 and Her4/ErbB4) and 13 secreted polypeptide ligands. EGFRs are overexpressed in many solid tumors, including breast, pancreas, head-and-neck, prostate, ovarian, renal, colon, and non-small-cell lung cancer. Such overexpression produces strong stimulation of downstream signaling pathways, which induce cell growth, cell differentiation, cell cycle progression, angiogenesis, cell motility and blocking of apoptosis.The high expression and/or functional activation of EGFRs correlates with the pathogenesis and progression of several cancers, which make them attractive targets for both diagnosis and therapy. Several approaches have been developed to target these receptors and/or the EGFR modulated effects in cancer cells. Most approaches include the development of anti-EGFRs antibodies and/or small-molecule EGFR inhibitors. This review presents the state-of-the-art and future prospects of targeting EGFRs to treat breast cancer.
Highlights
Despite the significant improvements in breast cancer detection and treatment, it remains the most life-threatening disease in women, with nearly 2.1 million new cases diagnosed in 2018, representing 25%of all cancers in women, and it is still responsible for more than 600,000 deaths annually worldwide [1].Breast cancer is a heterogeneous disease in which each tumor presents a different receptor expression profile
Binding of Panitumumab to EGFR1 inhibits the signaling cascade and blocks proliferation. It was approved by the FDA in 2006 for the treatment of epidermal growth factor receptor (EGFR)-positive metastatic colorectal carcinoma resistant to oxalaplatin, irinotecan- and fluoropyrimidine based therapies [56]
Zalutumumab is a human Monoclonal Antibodies (mAbs) with a high affinity to EGFR1 and is characterized by its low immunogenicity which improves its tolerance while retaining the induction of the antibody-dependent cellular toxicity (ADCC) [60,61]
Summary
Despite the significant improvements in breast cancer detection and treatment, it remains the most life-threatening disease in women, with nearly 2.1 million new cases diagnosed in 2018, representing 25%. Breast cancer is a heterogeneous disease in which each tumor presents a different receptor expression profile. Of breast cancer cases and accounts its heterogeneity, heterogeneity,three threereceptors receptors commonly overexpressed, namely. In 25% of the TNBC cases, EGFR1 over-expression is caused by its gene amplification genenot amplification and not due to activating mutations [8,9]. The correlation between overexpression of EGFR1 and downregulation of Her with a poor clinical outcome outcomehighlights highlightsthe the need a targeted therapy for increasing the efficacy andprofiles safety need forfor a targeted therapy for increasing the efficacy and safety profiles of the drugs by aiming for the cancer cells without affecting the healthy cells
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