Retinoblastoma

These analyses revealed that AMF directly targets smoothened (SMO) to disrupt the SHh signaling pathway, thereby suppressing RB stem cell (RBSC) self-renewal and tumor progression. This work uncovers a previously unreported mechanism by which AMF hinders RB development and highlights its potential as a promising therapeutic candidate for this aggressive pediatric cancer.

Patients with EGFR-mutant LUSC or LUAS had shorter overall survival on first-line osimertinib compared with those with EGFR-mutant LUAD...Combined EGFR and MET inhibition suppressed tumor growth in patient-derived xenograft models of LUSC transformation. Together, these findings highlight Rb pathway inactivation as a promoter of LUSC transformation in EGFR-mutant lung cancer and identify MET signaling as a therapeutic vulnerability that may suppress plasticity in this setting and extend response to targeted therapy.

In vivo, Orientin also suppressed tumor progression, promoted p16 and p21 expression, and inhibited CCNE/CCNA-CDK2 signaling. Orientin exerts anti-cancer effects in GC through triggering cellular senescence and cell cycle arrest, likely via activating p16/p21-Rb signaling axis and inhibiting the CCNE/CCNA-CDK2 pathway.

Upstream regulators of the homologous recombination (HR) repair pathway are promising targets for overcoming temozolomide (TMZ) resistance. Both compounds inhibited H3K27Ac and were detectable in orthotopic tumors by LC-MS/MS and significantly extended survival alone and in combination with TMZ. These findings suggest that the RBBP4/p300-axis is a key regulator of HR-mediated repair of TMZ-induced DSBs, and inhibition by either CCS1477 or NEO2734 may be beneficial as monotherapy, but further studies are needed to determine the benefit of combining these agents with TMZ.

Although genetic testing was not performed, bilateral disease strongly suggests germline RB1 mutation, a well-established risk factor for osteosarcoma. Persistent musculoskeletal symptoms in such patients warrant prompt radiologic evaluation to avoid diagnostic delay.

Understanding the underlying mechanisms involved in RB and exploring new treatment strategies is a crucial step toward developing more effective and less invasive therapeutic approaches that can improve patient outcomes. This review summarizes the significant genetic and epigenetic alterations involved in RB tumorigenesis, current therapeutic strategies, and future treatment prospects for patients with RB.

Furthermore, our results highlight the importance of offering targeted genetic testing and counseling to families with RB1 mutations. The identification of the somatic origin of this mutation was vital in ruling out the heritability of this condition in this specific patient.

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.