Recent Advances in Epidermal Growth Factor Receptor Inhibitors (EGFRIs) and their Role in the Treatment of Cancer: A Review

Abstract

Tyrosine kinases are known to play a role in tumour growth and proliferation, and they have become common drug targets. Tyrosine kinase inhibitors (TKIs) prohibit associated kinases from phosphorylating tyrosine residues in their substrates, preventing downstream signaling pathways from being activated. Multiple robust and well-tolerated TKIs targeting single or multiple targets, including EGFR, ALK, ROS1, HER2, NTRK, VEGFR, RET, MET, MEK, FGFR, PDGFR, and KIT, have been developed over the last two decades, contributing to our understanding of precision cancer medicine based on a patient's genetic alteration profile. The epidermal growth factor receptor (EGFR) family consists of four transmembrane tyrosine kinases (EGFR1/ErbB1, Her2/ErbB2, Her3/ErbB3, and Her4/ErbB4) and thirteen polypeptide ligands produced by them. Multiple solid tumours, including breast, pancreatic, head and neck, kidney, vaginal, renal, colon, and non-small cell lung cancer, overexpress EGFRs. Overexpression of these genes stimulates downstream signaling channels, causing cell proliferation, differentiation, cell cycle progression, angiogenesis, cell motility, and apoptosis inhibition. EGFRs' high expression and/or adaptive activation coincides with the pathogenesis and development of many tumours, making them appealing candidates for both diagnosis and therapy. Several strategies for targeting these receptors and/or the EGFR-mediated effects in cancer cells have been established. The majority of methods include the development of anti-EGFR antibodies and/or small-molecule EGFR inhibitors. This review presents the recent advances in EGFR TKIs and their role in the treatment of cancer.

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Integrated PBPK-EO modeling of osimertinib to predict plasma concentrations and intracranial EGFR engagement in patients with brain metastases

“…Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, accounting for more than 80% of all cases 1 . Within the NSCLC patient population, the Epidermal Growth Factor Receptor (EGFR) has emerged as a promising therapeutic target 2 . EGFR mutations play a crucial role as oncogenic driver alterations in NSCLC, occurring in about 10–15% of cases among Caucasians and at a higher frequency of up to 50% among East Asians 3 .…”

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