IDENTIFICATION OF THERAPEUTIC COMPOUNDS FOR BREAST CANCER: AN IN-SILICO APPROACH EXPLORING EGFR TARGETING INTERACTIONS OF KINASE INHIBITORS AND BIOACTIVE PHYTOCOMPOUNDS

Abstract

Introduction - One of the leading contributors in cancer-related mortality within female population is Breast Cancer (BC), which is a progressive disease and a lifelong susceptibility among females characterized by unrestrained cell proliferation, metastasizing to different parts of the body, impacting overall health and organ function. It stands out as the most predominant malignancies among female population across the globe, with millions of fresh cases getting diagnosed each year. Given the worldwide predominance of breast cancer, there is a crucial demand for innovative, potent and effective treatment strategies. Several overexpressed genes have been discovered in association with breast cancer, among them is EGFR (Epidermal Growth Factor Receptor). EGFR demonstrates pivotal role in progression or advancement of tumor and resistance to therapy. EGFR inhibition has been reported for therapeutic purpose in several variants of BC especially involving triple negative breast cancer (TNBC) making it one of the promising target molecule. Methodology - In this investigation, we executed the docking of EGFR protein utilizing FDA approved kinase inhibitor effective against cancers, alongside certain phytocompounds with anti-cancer properties as the target ligands, aiming for identification of potential therapeutic drug and comparative analysis among the natural compounds and TKIs. Molecular docking was executed utilizing PyRx and Biovia Discovery studio software for interpreting the potent drug candidate among the chosen ligands. Lipinski’s criteria of 5 and toxicity analysis was employed for assessing the drug-likeness and pharmacokinetic characteristic against breast cancer activity. The standard reference compound used in response to EGFR were Panaxadiol, Lapatinib, and Gefitinib. Results - Our investigation revealed, Psoralidin, Capmatinib, and Tucatinib as best docked and stably bound upon docking with chosen breast cancer target protein and TKIs performed better than phytocompounds. Limitations - The study proposes that the shortlisted phytocompounds and kinase inhibitors must undergo further in vitro and in vivo evaluation to unfold their effectiveness against breast cancer, demonstrating their potency to downregulate EGFR-linked cascades.