LSI Challenge: Health

Antibody-drug conjugates (ADCs) are a remarkable therapeutic strategy for the delivery of highly cytotoxic payloads to cancers utilizing binding to tumor-associated antigens. The deruxtecan (DXd)-based ADCs trastuzumab-DXd (T-DXd) and datopotamab-DXd (Dato-DXd) have demonstrated strong clinical anti-tumor activity. However, there is potential of enhancing the efficacy of these ADCs by exploiting the DNA damage response (DDR) pathways or by inhibiting pro-survival pathways associated with the antibody’s antigen. 

The hypothesis of this study is that a combinatorial approach may enhance the effectiveness of Dato-DXd in ovarian cancer and T-DXd in esophagogastric and endometrial cancers.