Targeted therapy of gastric cancer: The efficacy of fam-trastuzumab deruxtecan-nxki on HER۲-positive gastric cancer

Gastric cancer is one of the most prevalent and lethal cancers with a low survival rate in the world. Due to subtle symptoms of earlier disease and a low rate of regular screening, it is usually diagnosed at the advanced stage. Targeted therapy is considered a promising treatment option for patients with unresectable, advanced, or metastatic gastric cancer. Human epidermal growth factor receptor ۲ (HER۲) has attracted much attention among the many therapeutic targets that play a role in the progression of gastric cancer. HER۲ is a transmembrane glycoprotein with tyrosine kinase activity that belongs to the epidermal growth factor receptor family. This receptor is involved in controlling cell growth. HER۲ Overexpression or amplification has been found in advanced or metastatic gastric cancer. Several specific drugs have been developed to inhibit HER۲ activity, among them fam-trastuzumab deruxtecan-nxki (T-DXd) as a novel drug that has made a huge leap in treating HER۲-positive gastric cancer. T-DXd is an antibody-drug conjugate (ADC) that consists of two main parts, one is a HER۲-anti antibody called trastuzumab, and the other one is a cytotoxic agent called deruxtecan. These two parts are bound via an enzymatically cleavable tetrapeptide-based linker. Trastuzumab binds to HER۲ and suppresses the signaling pathways. Afterward, deruxtecan enters these cells and inhibits the activity of topoisomerase I, causing DNA damage, and leading to apoptotic cell death. T-DXd as a novel targeted drug with a specific characteristic not only causing increasing in overall survival (OS) in patients with HER۲-positive gastric cancer but also demonstrates a safety profile with a promising future, There are still concerns about adverse side effects, including Interstitial Lung Disease (ILD), that it should be accompanied by careful monitoring and proper administration schedule. Considering the significant advancements in molecular techniques and the classification of gastric cancer based on subtypes, the landscape of targeted therapy for gastric cancer looks promising. In this literature review, the study investigates HER۲ as a therapeutic target and the efficacy of fam-trastuzumab deruxtecan-nxki on HER۲-positive gastric cancer.

کلیدواژه ها:

Gastric cancer ، Targeted therapy ، HER۲-positive ، trastuzumab deruxtecan