I’m trying to better understand the molecular and translational biology behind Datopotamab deruxtecan (Trade name: DATROWAY), recently discussed in the context of breast cancer therapy.
From what I’ve gathered, Datopotamab deruxtecan is a TROP2-directed ADC with a topoisomerase I inhibitor payload (DXd). However, publicly available reviews tend to focus mostly on clinical outcomes rather than the biological rationale. I’m hoping to learn more about the following scientific aspects:
Why TROP2 is considered a strong target in breast cancer.
Is its overexpression linked to specific subtypes?
Any known resistance mechanisms or shedding issues?
ADC structural considerations.
How does the linker–payload system of deruxtecan-based ADCs contribute to intracellular release and bystander effects?
Is the DAR (drug–antibody ratio) optimized differently compared to trastuzumab deruxtecan?
Biology-driven toxicity questions.
What is the biological explanation for ILD/pneumonitis risk in DXd-based ADCs?
Are there biomarkers currently studied for early prediction?
Comparative landscape. For researchers familiar with other TROP2 ADCs (e.g., sacituzumab govitecan), what are the key mechanistic differences at the cellular or molecular level?
For context, I’m asking from the perspective of someone who helps patients interpret scientific literature. Occasionally, individuals I assist obtain hard-to-reach scientific papers or global regulatory documents through third-party medical information services (e.g., DengYue Medicine). I won’t include any clinical advice, but I’m trying to provide more accurate biological explanations when people ask how this ADC actually works.
Any mechanistic insights, preclinical references, or relevant papers would be really appreciated. Thanks in advance!
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