Retinal organoid screening reveals ABT-737 and luminespib as potential agents against a cone- precursor-derived subtype of retinoblastoma

Résumé fourni par la source

cone cells and strong apoptotic induction, evidenced by caspase-3 activation and Annexin V/7-AAD flow cytometry, without inducing necrosis. Single-cell RNA sequencing confirmed that both agents targeted the Rb-like proliferating cone precursors. Ocular pharmacokinetic modeling using pluripotent-stem-cell-derived retinal pigment epithelium (RPE) monolayers revealed limited permeability across the outer blood-retinal barrier for both drugs; however, luminespib showed moderate translocation, likely due to its lower molecular weight. In contrast, the uptake of ABT-737 by the retinal organoids was more efficient than that of luminespib. Together, these findings highlight ABT-737 and luminespib as potential therapeutic candidates against a cone-precursor subtype of Rb and demonstrate the utility of integrated retinal organoid and RPE models for preclinical drug screening and pharmacokinetic evaluation. However, validation in additional retinoblastoma subtypes beyond cone-precursor-derived tumors is essential to determine broader therapeutic applicability and efficacy. Future studies should prioritize testing these agents across diverse Rb genomic and phenotypic subtypes to address potential heterogeneity in treatment response.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.