Retinoblastoma

P=N/A, N=13, Active, not recruiting, Fundació Sant Joan de Déu | Recruiting --> Active, not recruiting | Phase classification: P1 --> PN/A | Trial completion date: Jun 2022 --> Jul 2024 | Trial primary completion date: Jun 2022 --> Jun 2024

Our data not only identified the prognostic/predictive significance of these key cell cycle regulators but also demonstrate the importance of sub-cellular localisation. CDK2 targeting in cyclin-E1-amplified OCs could be a rational approach.

P2, N=71, Active, not recruiting, The Hospital for Sick Children | Trial completion date: Dec 2023 --> Dec 2024

P=N/A, N=4351, Recruiting, Amsterdam UMC, location VUmc

P=N/A, N=607, Completed, Amsterdam UMC, location VUmc

The diagnosis and treatment of retinoblastoma necessitate consideration of numerous factors, including disease staging, germline mutation status, family psychosocial factors, and the resources available within the institution. This review has systematically compiled and categorized the latest developments in the diagnosis and treatment of retinoblastoma which enhanced the quality of care for this pediatric malignancy.

We conclude that HPV-positive non-OPSCC are associated with p16 overexpression and low levels of pRb and cyclin D1. High expression of pRb and cyclin D1 indicates HPV-negativity.

P1, N=44, Recruiting, Seattle Children's Hospital | Trial completion date: Jun 2038 --> Jun 2040 | Trial primary completion date: Jun 2024 --> Jun 2025

P3, N=179, Active, not recruiting, Sun Yat-sen University | Trial completion date: Dec 2023 --> Apr 2024 | Trial primary completion date: Dec 2023 --> Apr 2024

P=N/A, N=30, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Mar 2024 --> Mar 2025 | Trial primary completion date: Mar 2024 --> Mar 2025

By demonstrating that TSPAN8+SIRT6low myCAFs were tightly associated with unfavorable disease outcomes, we proposed that the combined regimen of anti-TSPAN8 antibody and SIRT6 activator MDL-800 is a promising approach to overcome chemoresistance. These findings highlight that senescence contributes to CAF heterogeneity and chemoresistance and suggest that targeting TSPAN8+ myCAFs is a promising approach to circumvent chemoresistance.

These findings provide novel insights into the mechanism by which HCA regulates adipogenesis and highlight the RPS6KA1/FoxO1 signaling axis as a therapeutic target for obesity.

In summary, our study clarifies the specific role of RB1 in hindbrain neural cell proliferation and morphogenesis by regulating the E2f3-Gbx1 axis and the Hdac1-Gbx2 axis. These findings provide a research paradigm for exploring the differential proliferation of neurons in various brain regions.

Our results indicate that miR-889-3p, which targets BMPR2 and promotes Rb growth by controlling the JNK/MAPK/ERK pathway, is an oncogene in Rb. These results suggested that the miR-889-3p/BMPR2 axis may be a new therapeutic target for Rb.

Notably, the great efficacy to activate immune responses is demonstrated in the patient-derived xenograft model and the patient-derived organoid model as well, revealing a clinical application potential. Overall, our study represents a promising therapeutic approach for targeting liver metastasis, remolding the tumor immune microenvironment (TIME), and enhancing the response of MSS/pMMR CCLM to boost ICB immunotherapy.

P=N/A, N=30000, Enrolling by invitation, RTI International | N=20000 --> 30000

Furthermore, miR-106a overexpression suppressed RB cell angiogenesis by downregulating HIF-1α expression level. NEAT1 promoted proliferation, invasion, and angiogenesis of RB cells through upregulation of HIF-1α expression level by sponging miR-106a, demonstrating that NEAT1 may be a novel target for RB treatment.

Overall, micron-grade silica particles induced lung fibrosis through exosomal miR-107 negatively regulating the cell cycle signaling pathway. These findings may open a new avenue for understanding how silicosis is regulated by exosome-mediated cell-to-cell communication and suggest the prospect of exosomes as therapeutic targets.

Collectively, these findings indicate that SET7/9 plays an oncogenic role in osteosarcoma by regulating CDK4-cyclin D1 complex interaction and function. The combination of SET7/9 and CDK4 inhibition may thus provide a novel effective therapeutic strategy for osteosarcoma with no significant toxicity.

Strikingly, acute lowering of lipid synthesis rapidly activates the PERK/ATF4 endoplasmic reticulum (ER) stress pathway that blocks cell-cycle entry by increasing p21 levels, decreasing Cyclin D levels, and suppressing Retinoblastoma protein phosphorylation. Together, our study identifies a rapid anticipatory ER lipid checkpoint in G1 that prevents cells from starting the cell cycle as long as lipid synthesis is low, thereby preventing mitotic defects, which are triggered by low lipid synthesis much later in mitosis.

Accordingly, we designed RB-linker-proteolysis-targeting chimera (PROTAC) molecules, which decreased TRIM24 protein levels and inactivated the mTOR signaling pathway, thereby inhibiting prostate cancer. Therefore, this study not only elucidates the novel function of RB but also provides a theoretical basis for the development of new drugs for treating prostate cancer.

Moreover, CDKG1 protein and mRNA were found to over-accumulate in tny1 cells suggesting that CDKG1 may be a direct target of repression by TNY1. Our data expand the potential roles of subscaling proteins outside the nucleus and imply a control mechanism that ties TNY1 accumulation to pre-division mother cell size.

The expression levels of NR1D1 and NR2E3 were decreased in RB and closely associated with the clinical stage and high invasion of the disease. These findings provide new insights into the mechanism of RB progression and suggest that NR1D1 and NR2E3 could be potential targets for treatment strategies.

P3, N=200, Active, not recruiting, Hospital JP Garrahan | Recruiting --> Active, not recruiting | Trial primary completion date: Dec 2023 --> Dec 2024

Understanding the molecular mechanisms of these genetic lesions and their effects within lung epithelial cells is of paramount importance, in order to tackle this aggressive and deadly lung cancer. The present review summarizes the current knowledge on p53 and Rb aberrations, their biological significance, and their prospective therapeutic potential, highlighting completed and ongoing clinical trials with agents that target downstream pathways.

Histopathologic risk factors such as massive choroidal invasion and post-laminar optic nerve help in predicting the occurrence of metastasis in children with RB, while presence of microscopic residual disease requires aggressive adjuvant treatment in eyes enucleated for group E RB. The review provides a consensus document on diagnosis and genetics of RB in India.

This study demonstrates that sequential exposure to CPT generates DR clones of Y79 cells, which could serve as an appropriate model to evaluate the efficacy of drugs. The sEVs-CPT were highly effective in enhancing cytotoxicity in DR-Y79 cells, and appear to hold promise as a novel complimentary drug delivery system.

We report the case of a baby boy with Rb and polydactyly exhibiting a 46, XY, 15pstk+ Karyotype. We discuss potential genetic factors related to both Rb and polydactyly. Furthermore, there is a need for further exploration into the impact of chromosomal polymorphisms in Rb with polydactyly.

Our results for the first time reveal that ZNF862 is localized in the cytoplasm of HGFs. ZNF862 can inhibit the proliferation of HGFs by inhibiting the p21-RB1 signaling pathway, and it also promotes the apoptosis of HGFs by enhancing the Bcl-xL-Caspase 3 signaling pathway.

We found that the Japanese cohort with ductal adenocarcinoma has unique features such as high frequency of alterations in tumor suppressor gene such as TP53 and RB1 , and lack DDR pathway alterations, suggesting the existence of regional and racial differences in genomic profiles. Genomic analysis using next-generation sequencing is expected to be useful in elucidating the pathogenesis of ductal adenocarcinoma, and further accumulation of cases is considered important.

The expression of farnesyltransferase β, which is essential for RAS maturation, was found to be downregulated following RB1 depletion also in an RBL2/p130-dependent manner. These findings unveiled an unexpected mechanism whereby normal mammary epithelial cells resist to tumor initiation upon RB1 LOF.

Additionally, inhibiting ATR activity reduced apoptosis resulting from both silencing NOL12 expression and UV exposure. Thus, NOL12 may protect against UV irradiation-induced retinal damage by inhibiting ATR activity.

Published under a CC BY 4.0 license. Test Your Knowledge questions for this article are available in the supplemental material.

Our study supports the previous reports that AH may be used as a source of tumor-derived cfDNA. This is the first report from South Asia on isolation and genetic analysis of cfDNA from AH of RB eyes and, therefore, a big step forward in paving the role of tumor genetics in RB. Further studies are required to elucidate concordance between the tumor and AH genetic profile.

Two of the mutant lines are compound heterozygous, with different in-del mutations in each of their alleles, while the third mutant line is homozygous, with identical edits in both alleles. All lines maintained their stemness, pluripotency, formed embryoid bodies with cell types of all three lineages, displayed a normal karyotype and lost RB1 expression.

P=N/A, N=2136, Completed, National Cancer Institute (NCI) | Active, not recruiting --> Completed

The distinct expression patterns and varying effects on the cell cycle suggest different functions for the various OsCYCD proteins. Our findings will enhance understanding of the CYCD family in rice and provide a preliminary foundation for the future functional verification of these genes.

Accordingly, IRF3 global knockout or conditional deletion in HSCs aggravated liver fibrosis, a process mitigated by the CDK4/6 inhibitor. These findings underscore a straightforward yet vital mechanism of cGAS-STING signaling in inducing cellular senescence and unveil its unexpected biology in limiting liver fibrosis.

P3, N=107, Active, not recruiting, St. Jude Children's Research Hospital | Trial completion date: Jan 2024 --> Jan 2025

CDKN2A is mediated by METTL14-m6A modified and restrains p53 pathway activation to accelerate the malignancy of RB. This points to the METTL14-m6A-CDKN2A-p53 pathway axis as a possible prospective target for the future RB treatment.

Subsequently, the DNAzymes can target two different mRNAs, thereby realizing fluorescence/MR bimodal imaging and dual-gene therapy. This study is expected to provide a reliable and valuable basis for ocular tumor theranostics.

P=N/A, N=44, Completed, Masonic Cancer Center, University of Minnesota | Recruiting --> Completed | N=20 --> 44