ArticleOncotarget2016
Dual inhibition of protein kinase C and p53-MDM2 or PKC and mTORC1 are novel efficient therapeutic approaches for uveal melanoma.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 56 citations in OpenAlex.
- Topotecan Synergizes with SP141 in the Management of Uveal Melanoma.bioRxiv : the preprint server for biology · 2026Article
- Harnessing p53 for targeted cancer therapy: new advances and future directions.Transcription · 2025Review
- Enhanced Everolimus Delivery: Development and Evaluation of a Nanosuspension Formulation.International journal of nanomedicine · 2025Article
- The role of signaling pathways mediated by the GPCRs CysLTR1/2 in melanocyte proliferation and senescence.Science signaling · 2024Review
- MDM2 Inhibitors for Cancer Therapy: The Past, Present, and Future.Pharmacological reviews · 2024Review
- CEP-1347 Dually Targets MDM4 and PKC to Activate p53 and Inhibit the Growth of Uveal Melanoma Cells.Cancers · 2023Article
- Patient-derived zebrafish xenografts of uveal melanoma reveal ferroptosis as a drug target.Cell death discovery · 2023Article
- A phase I trial of LXS196, a protein kinase C (PKC) inhibitor, for metastatic uveal melanoma.British journal of cancer · 2023Article
- Protein kinase inhibitor responses in uveal melanoma reflects a diminished dependency on PKC-MAPK signaling.Cancer gene therapy · 2022Article
- Protein kinase C targeting of luminal (T-47D), luminal/HER2-positive (BT474), and triple negative (HCC1806) breast cancer cells in-vitro with AEB071 (Sotrastaurin) is efficient but mediated by subtype specific molecular effects.Archives of gynecology and obstetrics · 2022Article
- Targeting p53-MDM2 interaction by small-molecule inhibitors: learning from MDM2 inhibitors in clinical trials.Journal of hematology & oncology · 2022Review
- Novel Treatments of Uveal Melanoma Identified with a Synthetic Lethal CRISPR/Cas9 Screen.Cancers · 2022Article
- Review
- Adjuvant crizotinib in high-risk uveal melanoma following definitive therapy.Frontiers in oncology · 2022Article
- Targeting Oncogenic GαCancers · 2021Review
- Review
- Dual Inhibition of Histone Deacetylases and the Mechanistic Target of Rapamycin Promotes Apoptosis in Cell Line Models of Uveal Melanoma.Investigative ophthalmology & visual science · 2021Article
- HighOncotarget · 2021Article
- Ubiquitin-proteasome system-targeted therapy for uveal melanoma: what is the evidence?Acta pharmacologica Sinica · 2021Review
- Hindsight: Review of Preclinical Disease Models for the Development of New Treatments for Uveal Melanoma.Journal of Cancer · 2021Review
Corrections and comments
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Authors and funding
16 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Uveal melanoma (UM) is the most common cancer of the eye in adults. Many UM patients develop metastases for which no curative treatment has been identified. Novel therapeutic approaches are therefore urgently needed. UM is characterized by mutations in the genes GNAQ and GNA11 which activate the PKC pathway, leading to the use of PKC inhibitors as a rational strategy to treat UM tumors. Encouraging clinical activity has been noted in UM patients treated with PKC inhibitors. However, it is likely that curative treatment regimens will require a combination of targeted therapeutic agents. Employing a large panel of UM patient-derived xenograft models (PDXs), several PKC inhibitor-based combinations were tested in vivo using the PKC inhibitor AEB071. The most promising approaches were further investigated in vitro using our unique panel of UM cell lines. When combined with AEB071, the two agents CGM097 (p53-MDM2 inhibitor) and RAD001 (mTORC1 inhibitor) demonstrated greater activity than single agents, with tumor regression observed in several UM PDXs. Follow-up studies in UM cell lines on these two drug associations confirmed their combination activity and ability to induce cell death. While no effective treatment currently exists for metastatic uveal melanoma, we have discovered using our unique panel of preclinical models that combinations between PKC/mTOR inhibitors and PKC/p53-MDM2 inhibitors are two novel and very effective therapeutic approaches for this disease. Together, our study reveals that combining PKC and p53-MDM2 or mTORC1 inhibitors may provide significant clinical benefit for UM patients.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.