GNA11 mutation

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.

Moreover, we discuss the role of SOX10-positive perivascular cells that may be implicated in the complex pathophysiology of GNAQ/GNA11-related entities. Understanding the common molecular foundation of these conditions opens new ways for research and treatment opportunities, potentially leading to more effective, personalized therapeutic strategies.

The recurrence of a choroidal melanoma is substantiated by the histopathological and molecular analyses, including the finding of a GNA11 mutation. This case exemplifies a remarkably delayed distant recurrence of a choroidal melanoma, which manifested clinically 40 years following enucleation.

We were able to successfully conduct NGS studies in paraffin-embedded material archived for 10 years using both middlesized (OPA) and large (OCA v3) NGS panels. The identified S3FB1 mutation helps to explain the onset of metastases, even though the patient had spindle cell predominant UM with BAP-1 preservation, which are normally associated with decreased metastases risk. Our case highlights the value of using large NGS panels to unravel the molecular landscape of UM and further understand this unique eye cancer.

The distinct genomic profiling in Japanese patients, including lower TMB, compared to Caucasians, is associated with poorer treatment outcomes. This result underscores the need for more effective therapeutic agents.

We examined the transcriptome of UM biopsies collected pre- and post-PKC inhibitor therapy and confirmed that MAPK, but not PI3K/AKT signalling, was inhibited early during treatment with the second-generation PKC inhibitor IDE196...We also show that re-activation of MAPK signalling has a dominant role in regulating PKC inhibitor responses in UM and that PI3K/AKT signalling diminishes UM cell sensitivity to PKC inhibitor monotherapy. Thus, combination therapies targeting PKC and PKC-independent signalling nodes, including PI3K/AKT activity, are required to improve responses in patients with metastatic UM.

P2, N=4, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: May 2024 --> Dec 2025

Baseline ctDNA and LDH are prognostic factors while ctDNA clearance might predict benefit from Tebe. Other analyses are ongoing to identify new predictive biomarkers.

P2, N=4, Active, not recruiting, National Cancer Institute (NCI) | N=35 --> 4

Although these subprotocols did not meet the primary end point for ORR, significant responses or prolonged SD noted in some disease subtypes warrants further investigation.

GNAQ and GNA11 mutations were identified to be the most frequent mutations among UM patients, with a mutual exclusivity relationship between the two genes. New therapeutic modalities should consider the comprehensive genomic profiling of UM patients to improve their overall survival rate and quality of life.