Eye Cancer

PLEK2 is upregulated in UVM and correlates with poor patient prognosis, likely influencing the calcium signaling pathway. PLEK2 represents a promising prognostic biomarker and therapeutic target for UVM.

CHEMBL82047 and CHEMBL381163 are ideal compounds for inhibiting MMP9. The findings of this study will contribute to the design and improvement of MMP9-targeting drugs.

Leveraging RB-mediated senescence presents promising opportunities for cancer therapy, including novel approaches in tumor immunotherapy designed to enhance treatment efficacy. This review highlights recent advancements in the RB signaling pathway, focusing on its roles in cellular senescence and tumor suppression, and discusses its potential to improve tumor management and clinical outcomes.

Although the bispecific tebentafusp is FDA-approved, immunotherapy has largely failed, likely given the poorly immunogenic nature of UM...In particular, the CPT1 inhibitor, etomoxir, induced propidium iodide uptake, caspase 3 cleavage and the release of HMGB1 and IL-1β, indicating that the observed cleavage of gasdermins led to pyroptosis...Together, these data show that metabolic inhibitors can induce pyroptosis in UM cell lines, potentially offering an approach to enhance inflammation-mediated immune targeting in metastatic UM patients. Implications: Induction of pyroptosis by metabolic inhibition may alter the tumor immune microenvironment and improve the efficacy of immunotherapy in uveal melanoma.

In this small cohort of patients with retinoblastoma, non-RB1 variants did not appear to augment tumorigenesis or disease progression. Larger studies are required to determine associations between specific variants and development of SMN.

P1, N=26, Completed, The Hospital for Sick Children | Recruiting --> Completed | Trial completion date: Oct 2030 --> Oct 2024 | Trial primary completion date: Oct 2025 --> Oct 2024

In this respect, RB1 loss has been implicated in the progression of MM through its influence on interleukin-6 (IL-6) secretion and cell proliferation. This review comprehensively summarizes the role of RB1 in MM and expounds on the potential of targeting RB1 as a therapeutic strategy for this malignancy.

P2, N=32, Recruiting, H. Lee Moffitt Cancer Center and Research Institute | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Dec 2024 --> Sep 2025

This supports the notion that it may be safe to reduce the length of surveillance for new tumours in familial retinoblastoma from 7 years of age.

A player in this process is the retinoblastoma 1 (RB1) protein, whose phosphorylation prompts MCIDAS activation. Overall, this study identifies a role for actin-based mechanical inputs to the nucleus as controlling factors in cell differentiation.

P=N/A, N=100, Active, not recruiting, University of Washington

P=N/A, N=108, Active, not recruiting, Jonsson Comprehensive Cancer Center | Recruiting --> Active, not recruiting

Sil and SLNP-Sil effectively inhibited U87 and U251 cell migration 24 h after treatment. Our results indicated that Sil and SLNP-Sil are promising therapeutic approaches against glioblastoma and merit in vivo experimental verification using orthotropic xenograft mouse models against glioblastoma.

P2, N=51, Active, not recruiting, Institut Curie | Recruiting --> Active, not recruiting | Trial completion date: Sep 2028 --> Nov 2026 | Trial primary completion date: Jan 2027 --> May 2025

Affected children present at an early age and advanced stages of disease. This case highlights that FEVR can have a highly asymmetric and advanced presentation at an early age and must be distinguished from retinoblastoma in the differential diagnosis of leukocoria.

Both treatment sequences are clinically feasible. A clinical benefit was noted in the sequential combination of ICIs followed by tebentafusp. This observation is limited by the retrospective nature of the study and merits further investigation in prospective clinical trials.

Notably, the system also shows an excellent in vivo safety profile. In conclusion, the CRISPR-ADAReader system represents a groundbreaking method for the detection and editing of RNA, offering a potent instrument for the customized and precise governance of cell behavior.

Immunohistochemically, the cells were positive for vimentin, neuron-specific enolase, and S100, and negative for cytokeratin AE1/AE3, Iba-1, CD204, MelanA, Sox10, and PNL2. Based on these findings, the lesion was diagnosed as an iridociliary adenoma with ballooning change.

P2, N=27, Active, not recruiting, Jose Lutzky, MD | Trial completion date: Dec 2026 --> Jan 2026 | Trial primary completion date: Dec 2024 --> Jan 2024

P2, N=6, Active, not recruiting, Providence Health & Services | Recruiting --> Active, not recruiting | N=30 --> 6 | Trial primary completion date: Jun 2025 --> Dec 2024

P2, N=85, Not yet recruiting, iOnctura

In this Review, I describe our current knowledge of genetic predisposition to childhood and adolescent cancers. Survival rates in children and adolescents with cancer and CPGs are often poor, necessitating better integration of genomic testing into clinical care to improve cancer prevention, surveillance and therapies.

P1, N=6, Active, not recruiting, Vastra Gotaland Region | Recruiting --> Active, not recruiting

Given UVM's limited options, our study highlights the potential of digitoxin as a promising novel therapeutic agent for this aggressive and rare ocular cancer. Our comprehensive approach is effective in identifying the potent, cancer-specific therapeutic agents from herbal plants.

P3, N=290, Recruiting, European Organisation for Research and Treatment of Cancer - EORTC | Not yet recruiting --> Recruiting

It is hypothesised that the balance of this signal is also dependent on the ability of cells to moderate the TF, and therefore on the level of damage. However, prolonged exposure of cells for example due to inflammation, leads to the dysregulation of the G1/S checkpoint by the tumour suppressors, leading to aberrant growth.

P1/2, N=253, Recruiting, Fusion Pharmaceuticals Inc. | Trial primary completion date: Jun 2024 --> Jun 2025

A recurrence of the disease was observed in 4 (0.06%) cases. New information on cancer biomarkers in non-melanoma eyelid skin carcinoma contributes to choosing a correct therapy with achieving good aesthetic results and a good survival rate.

In addition, we identified only three cases with two SMNs following RB diagnosis, with at least one of these being an EWS. This case broadens the clinical and genetic landscape of RB, demonstrates the importance of a multidisciplinary approach in these patients, and highlights genetic diagnosis as a mandatory feature for management.

Doravirine was particularly effective in reactivating apoptosis and reducing cell growth in highly proliferative resistant cells by increasing tumor-suppressor proteins p16Ink4a and p27Kip1. These findings suggest that antiretroviral drugs can influence apoptosis and cell proliferation in RAF-inhibitor-resistant melanoma cells, offering potential therapeutic strategies for overcoming drug resistance.

Moreover, bioactive Chaga components exerted a synergistic action with cisplatin and with trastuzumab in SK-BR-3 cells by inhibiting both HER2 and HER1 activation and displayed an immunomodulatory effect. Thus, Inonotus obliquus represents a source of triterpenoids that are effective against aggressive BC subtypes and display properties of targeted drugs.

The combination of alisertib and pembrolizumab was well tolerated and led to prolonged SD in some immunotherapy-resistant patients, supporting our hypothesis that Aurora kinase A inhibition can reverse immunotherapy resistance of retinoblastoma protein-deficient HNSCC.

In conclusion, results from the present study suggest that ELF1 is overexpressed in GC. ELF1 combined with MMP9 can serve as a predictor of malignant biological behavior in GC and therefore a prognostic indicator for patients, due to its association with the tumor microenvironment.

P3, N=40, Recruiting, Vastra Gotaland Region | Not yet recruiting --> Recruiting

These findings highlight distinct morphomolecular features in RB-lost p53abn EC and confirm the utility of RB IHC as a surrogate for molecular RB1 alterations. This is the first study to show the potential use of RB in prognostic refinement of p53abn EC, although validation is warranted.

For patients with incomplete tumor resection, close follow-up is necessary. Proton beam radiation therapy can be considered to prevent recurrence or metastasis if needed.

Our retinoblastoma programme demonstrated continued improved outcomes in terms of early detection, treatment, RB mutation detection, and eye preservation, despite the different challenges posed by the economic crisis and pandemic.

The combination of abemaciclib and fulvestrant has promising activity with durable responses in advanced or recurrent EC; a randomized trial is planned.

CRX transcriptionally activates TCF7 to promote the proliferation of RPE and RB cells in vitro. CRX is a potential target for RPE-based regenerative medicine. The potential risk of this strategy, tumorigenic potential, should be considered.

We also explore molecular and histological features of secondary resistance. Our case highlights that PD-1-resistant melanomas should be screened for GNAQ/11 mutations, as tebentafusp may be a treatment option in this extremely rare disease.

Furthermore, silencing YAP or treating with its inhibitor, Verteporfin, attenuated PD-L1 expression induced by Gq/G11 mutations, thereby enhancing T cell activation and T cell-mediated cytotoxicity. Collectively, this study reveals a potential role of Gq/G11 mutations on immune evasion of UM, a new mechanism of Gq/11 mutations-induced tumorigenesis, highlighting Gq/G11 and YAP as potential immunotherapeutic targets and suggesting Verteporfin as an adjuvant for immunotherapy of UM patients with GNAQ or GNA11 mutations.

Computed tomography (CT) scanning of the orbit revealed no extension, and positron emission tomography-computed tomography (PET-CT) showed no systemic involvement. The patient underwent surgical excision without adjuvant chemoradiation and has remained in clinical remission for five months.