A UH Cancer Center study indicates that breast cancer patients may achieve longer-lasting benefit from antibody-drug treatments if clinicians rotate to a different drug class after the initial therapy ceases to work.
Presented on December 10, 2025, at the San Antonio Breast Cancer Symposium, the findings show that in laboratory experiments and animal models, tumors that had become resistant to one antibody-drug conjugate (ADC) regained sensitivity when treated with a subsequent ADC that carried a different drug class.
ADC therapies work by using an antibody to deliver a potent anticancer drug straight to tumor cells. However, many breast cancer ADCs rely on the same DNA-targeting drug, and real-world experience has shown that using similar ADCs in sequence often yields limited additional benefit.
The UH researchers suggest this may be due to cross-resistance. In models of both HER2-positive and triple-negative breast cancer, switching from a DNA-targeting payload to a cell-division–blocking payload restored tumor control, even though the antibody continued to target the same cancer-cell marker.
“A straightforward takeaway is this: after a cancer progresses on one ADC, select the next ADC with a different type of drug,” said Jangsoon (Jason) Lee, associate professor and director of the UH Cancer Center Preclinical Core. “This strategy could help these advanced treatments keep working longer for patients.”
Naoto T. Ueno, UH Cancer Center director, added, “These findings show that drug resistance does not necessarily mark the end of the road for patients. Choosing the right kind of drug next could help more patients benefit from ADC therapies.”
The UH Cancer Center is collaborating with clinical partners to design studies that tailor the next ADC’s drug payload to the tumor’s resistance pattern, with the aim of extending the beneficial window of these treatments.
