Method Profile
Measure renal-cancer organoid viability and ferroptosis-associated redox responses after ALDH1L2 perturbation and drug treatment.
Preclinical study of ALDH1L2-associated sunitinib sensitivity and candidate combination activity.
Three renal cell carcinoma organoid lines from patients with poor sunitinib response; renal cancer cells and an organoid-derived xenograft provide separate follow-up systems.
48-hour organoid pharmacology, ALDH1L2 gain/loss comparisons and HA-1 combination testing. Docking, cellular thermal stability and surface plasmon resonance assess candidate interaction separately.
Organoid pharmacology
Sunitinib 0.1–1,000 μM with untreated control for the concentration response; 10 μM for 48 hours in follow-up. ATP-based viability, live/dead staining and redox measurements.
Mechanistic comparisons
ALDH1L2 overexpression or reduction, erastin challenge, and HA-1 plus sunitinib. Readouts include ROS, GPX4/SLC7A11, glutathione, NADP+/NADPH, Fe2+ and malondialdehyde.
Compare drug injury across ALDH1L2 states and matched treatment controls. Keep direct binding, protein abundance and enzyme inhibition as distinct claims; the last was not directly assayed.
Three donor-derived organoid lines; five separately examined paired clinical tissue samples; 24 xenograft mice, six per group.
Control versus ALDH1L2 perturbation, sunitinib alone versus combination, and erastin challenge.
ALDH1L2 overexpression reduced sunitinib-associated injury and oxidative changes, while reduction shifted responses oppositely. HA-1 bound ALDH1L2 with Kd 7.83 × 10⁻⁶ M and strengthened combination activity in culture. The HA-1 combination was not validated in vivo.
Primary study comparisons of the stated models, treatments and measurements.
Three renal cancer organoid models linked ALDH1L2 to redox changes and reduced sunitinib response. A candidate compound, HA-1, bound ALDH1L2 and strengthened the organoid response to sunitinib, while its mechanism, exposure and safety remain unresolved.
