Retinoblastoma

Conversely, BIRC5 knockdown induced G1 cell cycle arrest and increased apoptotic activity, accompanied by activation of checkpoint pathways. This study defines BIRC5 as a cell-state-specific regulator of malignant proliferation in retinoblastoma and provides a mechanistic rationale for targeting survivin in highly proliferative tumor subpopulations.

Although mice with Rb1 gene inactivation invariably develop pituitary adenomas, and some evidence suggests that a subset of pituitary adenomas have lack or reduced expression of Rb protein, to date no evidence has been reported that patients with germline mutations in the RB1 gene (that encodes for Rb protein) are at risk of developing pituitary adenomas. Here, we report the case of a patient with childhood (age 1 year) onset retinoblastoma because of a germline pathogenic variant of the RB1 gene who presented with a somatotropinoma diagnosed at a young age (20) and whose pituitary adenoma cells showed loss of expression of Rb protein by immunohistochemistry, suggesting a role of Rb in preventing the development of pituitary adenomas.

Survivors of hereditary retinoblastoma, caused by germline mutations in the RB1 gene, have a substantially increased risk of developing benign and malignant lipomatous tumors including atypical spindle cell/pleomorphic lipomatous tumor and dysplastic lipoma. This report describes the MRI findings of several such lesions in a survivor of bilateral retinoblastoma including features such as enhancement that might otherwise be concerning for higher-grade malignancy.

P=N/A, N=75, Recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: May 2026 --> May 2027 | Trial primary completion date: May 2026 --> May 2027

It also increased reactive oxygen species (ROS) production, caused DNA damage, inhibited DNA damage repair, activated the p53/p21 pathway, and ultimately induced apoptosis. These findings provide preclinical evidence that establishes abemaciclib as a promising novel treatment strategy for retinoblastoma.

We discuss actionable therapeutic opportunities, including compounds and degraders targeting PTM enzymes, and emphasize underexplored modifications such as SUMOylation, lactylation, and glycosylation that warrant systematic investigation in retinoblastoma. Finally, we integrate PTM biology with emerging immunotherapies and propose rational PTM-immunotherapy combinations and biomarker-guided translation to improve durable eye salvage and metastatic control.

Furthermore, this review explores the therapeutic potential of targeting m6A‑modifying enzymes (for example, small‑molecule inhibitors STM2457 and FB23‑2) and highlights challenges in tissue specificity, delivery systems and clinical translation. Future research should integrate multi‑omics technologies and precision intervention strategies to advance the application of m6A modification in the diagnosis and treatment of retinal diseases.

Together, these findings demonstrate that cfRNA- and ctcRNA-based liquid biopsy using CRX and RBP3 enables sensitive and dynamic detection of disseminated retinoblastoma, particularly in bone marrow, and supports its potential utility for MRD monitoring. Longitudinal patient analyses will be required to define prognostic thresholds and establish the clinical role of this approach in risk stratification and long-term surveillance.

Integrated multi-cohort transcriptomic analysis further revealed that PAX5-r induces a convergent expression profile relative to healthy individuals, characterized by dysregulation of the retinoblastoma transcriptional corepressor 1 (RB1) and p53 pathways and overexpression of nucleophosmin 1 (NPM1). These findings help to clarify core molecular mechanisms underlying PAX5-r-driven leukaemogenesis and highlight potential therapeutic vulnerabilities.

We discuss how tumor- and treatment-induced immune suppression shapes disease progression and therapeutic response, and how chemotherapy alters immune infiltration and checkpoint expression. Finally, we explore emerging immunotherapeutic and cell-based approaches, emphasizing the potential for combination therapies that integrate immune modulation to improve outcomes and reduce long-term toxicity in retinoblastoma.

P2, N=30, Recruiting, Targeted Therapy Technologies, LLC | Trial completion date: Nov 2028 --> Dec 2029 | Trial primary completion date: Nov 2028 --> Nov 2029

In conclusion, Hsa-let-7c-3p suppressed Rb cell proliferation/invasion and induced pyroptosis by negatively regulating ARHGAP11A. They are potential biomarkers of Rb.