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Transcriptional downregulation of MHC class I and melanoma de- differentiation in resistance to PD-1 inhibition
It is shown that resistance to anti-PD-1 blockade is associated with TGF-beta driven major histocompatibility complex I (MHCI) down-regulation and a de-differentiated phenotype in melanoma patients.
Oncogenic PI3K/AKT promotes the step-wise evolution of combination BRAF/MEK inhibitor resistance in melanoma
- M. Irvine, A. Stewart, Bernadette Pedersen, S. Boyd, R. Kefford, H. Rizos
- Biology, MedicineOncogenesis
- 1 September 2018
It is shown, that PI3K/AKT signalling via potent oncogenic PIK3CA and AKT3 mutants, is not sufficient to overcome proliferative arrest induced by BRAF/MEK inhibition, but rather enables the survival of a dormant population of MAPK-inhibited melanoma cells.
Melanoma Cell State-Specific Responses to TNFα
It is suggested that TNFα promotes dynamic changes in melanoma cells that may favor immunotherapy resistance, and is a poor inducer of antigen presentation molecules HLA-ABC and Hla-DR but readily induces the PD-L2 immune checkpoint in melanomas cells.
Interferon Signaling Is Frequently Downregulated in Melanoma
- S. Alavi, A. Stewart, R. Kefford, S. Y. Lim, E. Shklovskaya, H. Rizos
- Biology, MedicineFront. Immunol.
- 21 June 2018
Immune checkpoint inhibitors that block the programmed cell death protein 1/PD-L1 pathway have significantly improved the survival of patients with advanced melanoma. Immunotherapies are only…
Tumor MHC Expression Guides First-Line Immunotherapy Selection in Melanoma
It is demonstrated that the evaluation of tumor cell surface MHC-I expression aids in treatment selection, with combination immunotherapy providing clinical benefit over single-agent immunotherapy in M HC-I low melanoma with poor immune cell infiltration.
Uveal melanoma cell lines depend on multiple signaling pathways for survival
The sensitivity of GNAQ/11 mutation UM cell lines to 6 targeted drugs is heterogeneous and no single dominant signalling pathway was identified, suggesting that multiple, independent signal pathways contribute to the survival of UM.
Anchored Multiplex PCR Custom Melanoma Next Generation Sequencing Panel for Analysis of Circulating Tumor DNA
This study represents one of the first to successfully detect TERT promoter mutations in ctDNA from cutaneous melanoma patients using a targeted NGS panel.
Protein kinase inhibitor responses in uveal melanoma reflects a diminished dependency on PKC-MAPK signaling.
This study examined the signaling and functional effects of two PKC inhibitors in a panel of UM cell models and found that UM cell show complex, PKC-independent signaling pathways that contribute to their survival and resistance to targeted therapies.