Retinoblastoma

P=N/A, N=100, Recruiting, University of Washington | Active, not recruiting --> Recruiting

The findings in this study suggest that age at diagnosis may refine genetic risk stratification for metachronous bilateral conversion. RB1 variant-positive patients diagnosed at 9 months or later represent a very low-risk subgroup that may warrant surveillance deescalation, while rare late conversions in RB1 variant-negative patients necessitate continued long-term monitoring.

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.

Based on the in vitro drug responsiveness to carboplatin, five cultures were segregated as chemoresistant in which four of them were clinically known high-risk RB. One of the spheroids was further expanded and used to evaluate the in vitro efficacy of an FDA-approved drug to overcome resistance. Therefore, these RB patient-derived spheroids closely mirroring the clinicopathological features of the patient samples, represent a promising tool for drug screening and personalized RB therapy development.

This review summarizes RB pathogenesis, including RB1 loss, MYCN amplification, epigenetic dysregulation (e.g., METTL3-mediated m6A), and dysregulated pathways (PI3K/AKT/mTOR, Hedgehog), and highlights CRISPR-engineered organoids for identifying cone precursors as tumor origins and validating therapies (CDK4/6 inhibitors and sunitinib)...Future efforts should integrate multiomics, refine vascularization via 3D bioprinting, and develop immunocompetent models to address the disparity between preclinical research and clinical application. Organoid technology has the potential to advance personalized therapies and ultimately enhance the survival and quality of life of patients with RB worldwide.

P=N/A, N=3000, Recruiting, French Africa Pediatric Oncology Group | Trial completion date: Oct 2029 --> Dec 2030

In parallel, the expression of apoptosis-related genes was altered, as evidenced by the upregulation of the B-cell lymphoma 2 (Bcl-2)-associated X protein (Bax) and Caspase-3 and the downregulation of Bcl-2. Overall, these findings indicate that Hes enhances DOX efficacy by simultaneously engaging apoptotic and migration-associated molecular processes, supporting its potential role as a preclinical chemosensitizing agent that warrants further investigation in advanced experimental models.

While the use of EXOs presents a promising option for ocular treatment application, several factors complicate actual clinical translation, including standardization of isolation, scalable manufacture, and regulatory issues. In general, EXO-based nanomedicine may be a promising new direction for precision therapy and regenerative ophthalmology with the increasing introduction of synthetic and bioengineered EXOs introducing precursor paving new avenues for clinically scalable and biologically customizable EXO therapeutics.

In vivo, oAd-CMV-CALR suppresses Hepa1-6 xenograft growth, boosts CD8+ T-cell infiltration, and exhibits favorable safety. Collectively, our findings highlight oAd-CMV-CALR as a potential therapeutic approach to modulate the tumor microenvironment and improve cancer immunotherapy outcomes.

RNA analysis confirmed retention of intronic sequence (exonization), leading to unstable mRNA and/or truncated RB protein. This variant and the associated family history add to the existing body of literature to improve diagnostic genetic testing, clarify inheritance risks, and improve long-term outcomes for retinoblastoma patients.

P2, N=26, Recruiting, Children's Oncology Group | Trial completion date: Dec 2026 --> Mar 2028 | Trial primary completion date: Dec 2026 --> Mar 2028