Pharmacology of Epidermal Growth Factor Inhibitors

Abstract

Research into the molecular bases of malignant diseases has yielded the development of many novel agents with potential antitumor activity. Evidence for a causative role for the epidermal growth factor receptor (EGFR), which is now regarded as an excellent target for cancer chemotherapy in human cancer, leads to the development of EGFR inhibitors. Two classes of anti-EGFR agents are currently in clinical use: monoclonal antibodies directed at the extracellular domain of the receptor, and the low-molecular-weight receptor tyrosine kinase inhibitors acting intracellularly by competing with adenosine triphosphate for binding to the tyrosine kinase portion of the EGFR. The effect on the receptor interferes with key biological functions including cell cycle arrest, potentiation of apoptosis, inhibition of angiogenesis and cell invasion and metastasis. Cetuximab, a monoclonal antibody, and the receptor tyrosine kinase inhibitors gefitinib and erlotinib are currently approved for the treatment of patients with cancer. New agents with clinical activity are entering the clinic, and new combinatorial approaches are being explored with the aim of improving the potency and pharmacokinetics of EGFR inhibition, to increase the synergistic activity in combination with chemotherapy and overcome resistance to the EGFR inhibitors.

ASC, a Bioactive Steroidal Saponin from Ophitopogin japonicas, Inhibits Angiogenesis through Interruption of Src Tyrosine Kinase‐dependent Matrix Metalloproteinase Pathway

“…Cell cycle progression regulation is a vital therapeutic strategy for vascular proliferative disease such as tumour angiogenesis . From fig.…”

Effects of an epidermal growth factor receptor‐based cancer vaccine on wound healing and inflammation processes in murine experimental models

“…In tumourigenesis, EGFR expression and its downstream growth promoting processes are altered, causing metastasis and unregulated cell growth (4). EGFR is involved in cancer cells' distinctive properties.…”

Systematic review and meta‐analysis of the risk of severe and life‐threatening thromboembolism in cancer patients receiving anti‐EGFR monoclonal antibodies (cetuximab or panitumumab)

“…This results in down-regulation of EGF receptors and modulation of pivotal processes impacting on tumour growth and progression such as angiogenesis, induction of apoptosis, tumour invasiveness and metastatic spread. 13,14 For these reasons, EGFR is considered as a prominent therapeutic target for MoAbs-based immunotherapy in cancer. 15,16 The anti-EGFR antibodies cetuximab and panitumumab are effective in different lines of treatment and in several combinations in the management of neoplasia such as colorectal cancer.…”