ArticleCancer gene therapy2022
Protein kinase inhibitor responses in uveal melanoma reflects a diminished dependency on PKC-MAPK signaling.
Article in Cancer gene therapy, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 23 citations in OpenAlex.
- Oncogenic Gα signaling requires AP-3-dependent recruitment to the endolysosomal compartment.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- The role of signaling pathways mediated by the GPCRs CysLTR1/2 in melanocyte proliferation and senescence.Science signaling · 2024Review
- Single-cell RNA sequencing reveals melanoma cell state-dependent heterogeneity of response to MAPK inhibitors.EBioMedicine · 2024Article
- Transactivation of Met signaling by oncogenic Gnaq drives the evolution of melanoma in Hgf-Cdk4 mice.Cancer gene therapy · 2024Article
- Heterogeneity and molecular landscape of melanoma: implications for targeted therapy.Molecular biomedicine · 2024Review
- Stereotactic radiotherapy for uveal melanoma: A case report.Molecular and clinical oncology · 2024Article
- A centrosome-related gene signature for predicting the overall survival of uveal melanoma.Translational cancer research · 2024Article
- PKC-independent PI3K signalling diminishes PKC inhibitor sensitivity in uveal melanoma.Oncogenesis · 2024Article
- High-throughput chemogenetic drug screening reveals PKC-RhoA/PKN as a targetable signaling vulnerability in GNAQ-driven uveal melanoma.Cell reports. Medicine · 2023Article
- Oncogenic Gαq activates RhoJ through PDZ-RhoGEF.International journal of molecular sciences · 2023Article
- Resistance to immune checkpoint therapies by tumour-induced T-cell desertification and exclusion: key mechanisms, prognostication and new therapeutic opportunities.British journal of cancer · 2023Review
- LXS196 for Metastatic Uveal Melanoma - finally some progress.British journal of cancer · 2023Article
- Darovasertib, a novel treatment for metastatic uveal melanoma.Frontiers in pharmacology · 2023Review
- KDOAM-25 Overcomes Resistance to MEK Inhibitors by Targeting KDM5B in Uveal Melanoma.BioMed research international · 2022Article
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Uveal melanoma (UM) is a rare cancer arising from melanocytes in the uveal tract of the eye. Despite effective primary treatment, there is no approved therapy for metastatic UM and prognosis and survival remain poor. Over 90% of UM are driven by mutations affecting the Gα subunits encoded by the GNAQ and GNA11 genes. These mutations activate downstream and targetable signaling pathways, including the protein kinase C (PKC) cascade. PKC inhibitors have been used in clinical trials for metastatic UM but have shown limited efficacy. In this study, we examined the signaling and functional effects of two PKC inhibitors (AEB071 and IDE196) in a panel of UM cell models. In response to PKC inhibition, all UM cell lines showed potent suppression of PKC activity, but this was not sufficient to predict PKC inhibitor sensitivity and only two UM cell lines showed substantial PKC inhibitor-induced cell death. The differences in UM cell responses to PKC inhibition were not attributable to the degree or timing of PKC suppression or inhibition of the downstream mitogen-activated protein kinase (MAPK) or phosphatidylinositol-3-kinase (PI3K) pathways. Instead, UM cell show complex, PKC-independent signaling pathways that contribute to their survival and resistance to targeted therapies.
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