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UH Cancer Center
A University of Hawaiʻi Cancer Center study suggests that breast cancer patients may benefit longer from antibody-drug treatments if doctors switch to a different drug type after the first one stops working.
Presented December 10, 2025, at the San Antonio Breast Cancer Symposium, the research shows that in laboratory and animal models, tumors that stopped responding to one antibody-drug conjugate (ADC) regained sensitivity when treated with a follow-up ADC carrying a different drug class.
ADCs work by using an antibody to guide a potent cancer drug directly to tumor cells. Many breast cancer ADCs, however, use the same DNA-targeting drug type, and clinical experience has shown that using similar ADCs back-to-back often provides limited benefit.
The UH team found this may be due to cross-resistance. In models of both HER2-positive and triple-negative breast cancer, switching from a DNA-targeting drug to a cell-division–blocking drug restored tumor control, even though the antibody was still hitting the same cancer-cell marker.
“A simple takeaway is this: After a cancer progresses on one ADC, choose the next ADC with a different kind of drug,” said Jangsoon (Jason) Lee, associate professor and director of the UH Cancer Center Preclinical Core. “This drug-guided approach could help these smart treatments work longer for patients.”
“These findings show that drug resistance is not necessarily the end of the line for cancer patients,” added Naoto T. Ueno, UH Cancer Center director. “Choosing the right kind of drug next could help more patients benefit from ADCs.”
The UH Cancer Center is now working with clinical partners to design studies that match the next ADC’s drug payload to how a patient’s tumor becomes resistant, aiming to extend treatment benefit.