Publication Highlight: Combined KRAS-MAPK pathway inhibitors and HER2-directed drug conjugate is efficacious in pancreatic cancer

Guest Author: Ashenafi Bulle, Ph.D., Washington University School of Medicine in St. Louis

In this work, we shed light on the significance of drug combinations in fighting therapeutic resistance in pancreatic cancer. We developed MAPK inhibitor-based therapeutic combinations that are grounded in solid scientific rationale. Specifically, MAPK inhibitors combined with trastuzumab deruxtecan, an anti-HER2 antibody conjugated with cytotoxic chemotherapy, led to sustained tumor regression in most tested patient-derived xenografts (PDXs) without causing noticeable toxicity.

This work has been provisionally approved for clinical trial by the NCI Experimental Therapeutics Clinical Trials Network (ETCTN) under the study title “Phase I/II Study of the MEK Inhibitor Mirdametinib Plus DS-8201a in KRAS-Mutant, HER2-Expressing Pancreatic Ductal Adenocarcinoma.” We hope this work successfully passes all necessary clinical trials and becomes available for patients in clinical settings. Special thanks go to all researchers who contributed to this exciting project.