Honolulu scientists at the University of Hawaiʻi Cancer Center say a small change to a big-ticket cancer drug could make a major difference for patients whose tumors have stopped responding. Their move: when a breast tumor becomes resistant to an antibody-drug conjugate, or ADC, swap out the toxic payload attached to the antibody instead of abandoning ADCs altogether.
In lab dishes and mouse models, that simple switch restored tumor control in cancers that had already learned how to shrug off two widely used ADCs. The work, unveiled this week at a major breast cancer meeting, suggests oncologists might soon have a straightforward rule of thumb for picking the next ADC after a patient’s disease progresses.
What the lab work showed
The UH team engineered breast cancer models that had become resistant to two commonly used ADCs and saw that resistance spill over when both drugs carried the same active ingredient. When the researchers changed the payload from a DNA-targeting topoisomerase-I inhibitor to a drug that blocks cell division, tumor control came back in both cell cultures and mice.
The findings were reported in a press release from University of Hawaiʻi at Mānoa and presented on December 10, at the San Antonio Breast Cancer Symposium.
Real-world data lines up with the lab
Clinical data have hinted at the same pattern. When patients receive a second ADC, it tends to work less well if it uses the same type of payload as the first. In a multi-center retrospective analysis reported in PubMed Central, patients whose second ADC carried a different class of drug enjoyed longer progression-free survival than those who stayed with a similar payload…