Developmental reprogramming underlies chemotherapy resistance in favorable-histology Wilms tumor - PubMed
3 hours ago
- #ABCB1
- #Wilms tumor
- #chemotherapy resistance
- Developmental reprogramming contributes to chemotherapy resistance in favorable-histology Wilms tumor (FHWT).
- Patients with relapsed or blastemal-predominant FHWT post-chemotherapy often have poor outcomes.
- A patient-derived xenograft model (KT-47) was used to study resistance to vincristine, actinomycin-D, and doxorubicin (VAD).
- Multi-omics analyses showed chromatin and transcriptional changes, including altered H3K4me3 and H3K27me3 levels at stem cell and nephrogenesis genes.
- LIN28B is the most upregulated resistance-associated gene, linked to MYCN copy gain and chromatin remodeling.
- ABCB1 expression correlates with interchromosomal enhancer interactions and mediates chemotherapy resistance in vitro.
- Resistance involves de-differentiation to a stem-like state, driven by ABCB1 upregulation.
- Targeting chromatin regulation and drug efflux may be effective against therapy-resistant Wilms tumor.