Paolo Tarantino and Naoto Ueno: Why Traditional Biomarkers Fail to Predict ADC Efficacy
Paolo Tarantino and Naoto Ueno

Paolo Tarantino and Naoto Ueno: Why Traditional Biomarkers Fail to Predict ADC Efficacy

Paolo Tarantino, Research Fellow Dana-Farber Cancer Institute and Harvard Medical School, shared a post by Naoto Ueno, Director of the University of Hawaii Cancer Center, on X, adding:

”One key issue is that <1% of the ADC actually distributes to the tumor

Target expression attempts to predict the benefit from that 1%

Innovative biomarkers are needed to predict benefit from the remaining 99% that distributes across the rest of the body.”

Quoting Naoto Ueno’s post:

Both ASCENT-04 and ASCENT-03 efficacy is lbiomarker independent. Is this surprising? Not really. We have seen a similar pattern across the DESTINY-Breast studies, where no biomarker has been statistically meaningful enough to clearly define who benefits.

This may be a fundamental feature of ADC biology. ADCs are not classic targeted therapies in the narrow sense. They use the antibody to deliver a potent payload, and once enough drug reaches the tumor, the payload can effectively annihilate cancer cells.

That is why expression level, BRCA mutation status, or HER2-low versus HER2-ultralow may not always behave as clean predictive biomarkers.”

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