A Review on Anticancer Potential and Structure-Activity Relationships (SAR) of Novel EGFR/HER2 Inhibitors

Abstract: Human Epidermal Growth Receptor (HER) plays an important role in cell signalling pathways and influences different cell functioning like angiogenesis, apoptosis, metastasis, and growth of cells. Their family includes four members with structural similarities, named EGFR/HER1, HER2, HER3, and HER4. Overexpression of these receptors is responsible for the development of cancer. EGFR/HER2 dual inhibitors, approved by the US FDA (Food and Drug Administration), include lapatinib, afatinib, neratinib, dacomitinib, etc., but these drugs lack selectivity, specificity, and undesirable adverse effects. The ultimate challenges in developing lead compounds for EGFR/HER2 dual inhibitors include achieving precision, and minimising toxicity and drug resistance. This inspires medicinal and organic chemists to design new molecules. The present manuscript focuses on the identification and development of therapeutic molecules that can inhibit the target proteins EGFR/HER2 and can further be used for the treatment of breast and lung malignancies. It also highlights the development of EGFR/HER2 dual inhibitors that belong to different structural classes like pyrimidine, quinazoline, pyridine, benzimidazole, and quinoline etc. Various parameters, such as Structure-Activity Relationships (SAR), clinical trials data, patent filed, and the molecular docking study of the most potent compounds provide a valuable asset for further designing and discovering new EGFR/HER2 dual inhibitors with potential therapeutic significances for cancer treatment.