A Review on EGFR-Tyrosine Kinase Inhibitors and their Resistance Mechanisms.

backgroundAn essential component of cell development, proliferation, and survival is the transmembrane receptor known as the epidermal growth factor receptor (EGFR). Dysregulated EGFR signalling is an appealing pathway that has been linked to the genesis and progression of several cancer types. EGFR tyrosine kinase inhibitors (TKIs) are targeted drugs that show promise in the fight against cancer. EGFR tyrosine kinase inhibitors obstruct cancer growth and survival signalling pathways by blocking the receptor's tyrosine kinase domain. Patients with non-small cell lung cancer (NSCLC) that have EGFR mutations have shown increased progression-free survival and overall survival rates when treated with EGFR TKIs as compared to conventional chemotherapy, according to many clinical studies.

objectivesThis review is aimed to present the journey of EGFR-tyrosine kinase inhibitors, their signalling cascade, and various resistant mechanisms.

methodsThe literature search was carried out on electronic databases like PubMed, Medline, etc., by employing search keywords, such as EGFR, EGFR inhibitors, cancer, tyrosine kinase, etc., and data on EGFR signaling pathways and the types of potential inhibitors in a hierarchical manner, followed by various resistance mechanisms that have emerged, were collected.

resultsDrug resistance is still an issue in long-term therapy of patients, even though EGFR TKIs provide substantial therapeutic advantages. Common routes of resistance to EGFR TKIs include acquired resistance mechanisms, which include the development of secondary EGFR mutations and the activation of alternative signalling pathways. To improve the therapeutic effectiveness of EGFR TKIs, future research will center on searching indicators of response and resistance, finding ways to employ these medicines most effectively, and creating new treatment approaches.

conclusionThis review provides insight into the use of EGFR kinase inhibitors for treating cancer patients and outlines potential advancements in current therapies to develop more effective molecules.