Monoclonal antibodies, small molecule inhibitors and antibody-drug conjugates as HER2 inhibitors

2020 ◽  
Vol 27 ◽  
Author(s):  
Xiu-Fang Li ◽  
Chen-Fu Liu ◽  
Guo-Wu Rao
Keyword(s):  
Monoclonal Antibodies ◽  
Small Molecule ◽  
Small Molecule Inhibitors ◽  
Growth Factor Receptor ◽  
Research Progress ◽  
Antibody Drug Conjugates ◽  
Drug Conjugates ◽  
Her 2 ◽  
Epidermal Growth ◽  
Antibody Drug

: Overexpression of human epidermal growth factor receptor (HER)-2 is found in a variety of cancers, often portending poor clinical outcomes. Therefore, HER2 is an attractive target for treatment. This review describes the research progress of HER2 targeted inhibitors in recent years. Excellent reviews are available, so we focus on the development, mechanisms of action, and structure-activity relationships of different types of inhibitors, including monoclonal antibodies, small molecule inhibitors, and antibody-drug conjugates (ADCs). In addition, the differences among them are compared.

Cancer-targeting Antibody–Drug Conjugates: Site-specific Conjugation of Doxorubicin to Anti-EGFR 528 Fab' through a Polyethylene Glycol Linker

2011 ◽  
Vol 64 (6) ◽  
pp. 779 ◽  
Author(s):  
Lisa P. T. Hong ◽  
Judith A. Scoble ◽  
Larissa Doughty ◽  
Gregory Coia ◽  
Charlotte C. Williams
Keyword(s):  
Polyethylene Glycol ◽  
Growth Factor Receptor ◽  
Antibody Fragment ◽  
Aqueous Solubility ◽  
Cancer Targeting ◽  
Antibody Activity ◽  
Antibody Drug Conjugates ◽  
Drug Conjugates ◽  
Epidermal Growth ◽  
Antibody Drug

Antibody–drug conjugates have been prepared to examine the effect that attaching small-molecule drugs to an antibody fragment has on antibody activity. The anticancer drug doxorubicin was covalently attached through a polyethylene glycol linker to a cancer-targeting, anti-epidermal growth factor receptor antibody fragment (Fab′). The reactivity of maleimide was compared with a substituted maleimide derivative (citraconimide) in conjugation reactions with cysteine residues on a Fab′. Introduction of polyethylene glycol increased aqueous solubility of the cytotoxic drug, which led to an improvement in overall yield of the conjugation reaction with the antibody fragment. Antibody–drug conjugates prepared retained activity of the parent antibody, as determined by antigen binding experiments measured by surface plasmon resonance.

scholarly journals Antibody–drug conjugates as novel anti-cancer chemotherapeutics

2015 ◽  
Vol 35 (4) ◽  
Author(s):  
Christina Peters ◽  
Stuart Brown
Keyword(s):  
Monoclonal Antibodies ◽  
Small Molecule ◽  
Current Knowledge ◽  
Cytotoxic Agent ◽  
Cancer Drugs ◽  
Antibody Drug Conjugates ◽  
Cancer Chemotherapeutics ◽  
Drug Conjugates ◽  
Anti Cancer ◽  
Antibody Drug

Antibody drug conjugates (ADCs) are an efficacious class of anti-cancer drugs that comprise monoclonal antibodies (mAbs) conjugated to small-molecule cytotoxic agent via a stable linker. This review summarizes the current knowledge and developments in the field of ADCs.

scholarly journals Emerging Targeted Therapies for HER2 Positive Gastric Cancer That Can Overcome Trastuzumab Resistance

Cancers ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 400 ◽  
Author(s):  
Seiichiro Mitani ◽  
Hisato Kawakami
Keyword(s):  
Gastroesophageal Junction ◽  
Treatment Strategies ◽  
Growth Factor Receptor ◽  
Trastuzumab Resistance ◽  
Her2 Positive ◽  
Drug Conjugates ◽  
Gastroesophageal Junction Cancer ◽  
Development Of Resistance ◽  
Epidermal Growth ◽  
Antibody Drug

Trastuzumab, a monoclonal antibody to human epidermal growth factor receptor 2 (HER2), has improved survival in patients with HER2-positive advanced gastric or gastroesophageal junction cancer (AGC). The inevitable development of resistance to trastuzumab remains a problem, however, with several treatment strategies that have proven effective in breast cancer having failed to show clinical benefit in AGC. In this review, we summarize the mechanisms underlying resistance to HER2-targeted therapy and outline past and current challenges in the treatment of HER2-positive AGC refractory to trastuzumab. We further describe novel agents such as HER2 antibody–drug conjugates that are under development and have shown promising antitumor activity in early studies.

Translational aspects of biologicals: monoclonal antibodies and antibody-drug conjugates as examples

2021 ◽  
pp. 329-350
Author(s):  
Sophia N. Karagiannis ◽  
Ricarda M. Hoffmann ◽  
Mano Nakamura ◽  
Silvia Crescioli ◽  
Heather J. Bax ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Antibody Drug Conjugates ◽  
Drug Conjugates ◽  
Antibody Drug
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