Josh Drago, MD, MS
@joshdragomd.bsky.social
Breast Cancer Specialist
Clinical and Translational Investigator
Memorial Sloan Kettering Cancer Center
Clinical and Translational Investigator
Memorial Sloan Kettering Cancer Center
ADC resistance is likely heterogeneous, and the phenomena above may explain only a portion of cases. But these early clues can inform prospective trail efforts, as well as ADC sequencing strategies. There is much more to come!
November 10, 2025 at 4:55 PM
ADC resistance is likely heterogeneous, and the phenomena above may explain only a portion of cases. But these early clues can inform prospective trail efforts, as well as ADC sequencing strategies. There is much more to come!
To overcome this, we investigated giving low-dose multi-target ADC combinations, which ‘hedges’ against target-mediated resistance and allows for more consistent payload delivery.
November 10, 2025 at 4:55 PM
To overcome this, we investigated giving low-dose multi-target ADC combinations, which ‘hedges’ against target-mediated resistance and allows for more consistent payload delivery.
We modeled HER2 loss in isogenic laboratory models, which clearly compromised T-DXd internalization and cytotoxicity, leading to drug resistance.
November 10, 2025 at 4:55 PM
We modeled HER2 loss in isogenic laboratory models, which clearly compromised T-DXd internalization and cytotoxicity, leading to drug resistance.
More broadly, distinct HER2 downregulation was observed in a significant subset of patients with breast cancer treated with T-DXd, and seems more prevalent/pronounced in patients with HER2-low disease. This trend was not observed with Sacituzumab Govitecan in our cohort.
November 10, 2025 at 4:55 PM
More broadly, distinct HER2 downregulation was observed in a significant subset of patients with breast cancer treated with T-DXd, and seems more prevalent/pronounced in patients with HER2-low disease. This trend was not observed with Sacituzumab Govitecan in our cohort.
We report three cases of resistance to T-DXd underpinned by mutations in the trastuzumab binding domain. These cases are rare, but illustrative of the evolutionary pressure generated by a highly effective HER2-targeted therapy.
November 10, 2025 at 4:55 PM
We report three cases of resistance to T-DXd underpinned by mutations in the trastuzumab binding domain. These cases are rare, but illustrative of the evolutionary pressure generated by a highly effective HER2-targeted therapy.