Developing EGFR and c-MET pathway inhibitors;Implication for targeted therapies in triple-negativebreast cancer

Triple negative breast cancer (TNBC) is defined by the absenceof oestrogen receptor, progesterone receptor and HER۲ expressionat IHC analysis. Agents that target estrogen receptors (ER)and HER۲ are among the most successful cancer therapeutics.As our understanding of tumor biology improves, novel targetsare being identified.Notably,inhibitors against several pathwayshave demonstrated promising activity in clinical trials.RTKsare essential in carcinogenesis and act as therapeutic targets incancer. This study was performed using the collected article inEnglish that was available on details of the main topic from۲۰۰۰ to ۲۰۲۱ in Scopus, PubMed, and Web of Science withkeywords breast cancers, TNBC, targeted therapy, EGFR receptor,and RTK receptor.Articles were selected based on theexclusion criteria and, after reviewing, were included in thestudy. Recently, studies have shown that RTKs are often overexpressedin TNBC cells.Dysregulation of multiple RTKs, includingFGFR۱, EGFR, and HGFR, also called c-Met, is oneof the significant molecular abnormalities in TNBC.However,the results show that anti-RTK drugs are ineffective when usedalone and toxic when combined.Therefore, to solve this problem,it is necessary to use a drug that can bind to essential typesof RTK and, at the same time, is non-toxic and effective. Moreover,EGFRs are successful therapeutic targets in other cancersbut have yet to be thoroughly tested in TNBC. Cross-resistanceto EGFR and MET in treatment resistance to EGFR inhibitorsin colon and lung cancer has been previously shown. InEGFR,TNBC is phosphorylated in the presence of the inhibitor,and its continuous phosphorylation is associated with TKI resistance.This resistance to EGFR inhibition may occur throughMET-EGFR crosstalk; Therefore,it is essential that in order todevelop effective therapeutic strategies, both the inhibitor targetRTK and their combined inhibition can be effective in reducingthe severity of the disease in TNBC.

کلیدواژه ها:

breast cancers ، TNBC ، targeted therapy ، EGFR receptor ، RTK receptor