TRASTUZUMAB DERUXTECAN: NOVEL ANTIBODY-DRUG CONJUGATE TARGETING HER2 IN PATIENTS WITH GASTRIC ADENOCARCINOMA

Abstract

Gastric cancer (GC) is one of the main causes of death from cancer with a multifactorial origin and is characterized by the expression of a gene known as HER2. This gene promotes cell proliferation and prevents apoptosis of cancer cells, facilitating uncontrolled cell growth. Trastuzumab Deruxtecan (T-DXd) is a drug for the treatment of tumors with a heterogeneous expression of HER2 that are resistant to conventional anti-HER2 therapy. It is believed that the positive results obtained from Trastuzumab Deruxtecan in the treatment ofgastric cancer are related to its potent inhibitory effect of topoisomerase I, the stability of the linker in plasma, as well as its bystander effect. Furthermore, the drug is more efficiently delivered to its target (tumor cell), resulting in a higher concentration of the cytotoxic agent at the site of action. Another point to highlight is that trastuzumab deruxtecan has benefits in treating breast cancer compared to other anti-HER2 therapies since more patients using this drug presented positive responses compared to trastuzumab emtansine (TDM1), in addition to presenting longer survival and fewer adverse effects. Thus, this literature review shows that T-DXd is a promising therapy of extreme importance and with great capability to respond to cancers with low expression of HER2 and to HER2-positive cancers that are insensitive to the trastuzumab emtansine drug.