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Distinct Immune Cell Populations Define Response to Anti-PD-1 Monotherapy and Anti-PD-1/Anti-CTLA-4 Combined Therapy.
BRAF Inhibitor Resistance Mechanisms in Metastatic Melanoma: Spectrum and Clinical Impact
Selecting sequential drugs based on the molecular characteristics of a single progressing biopsy is unlikely to provide improved responses, and first-line therapies targeting multiple pathways will be required.
WNT5A enhances resistance of melanoma cells to targeted BRAF inhibitors.
It is suggested that chronic BRAF inhibition elevates WNT5A expression, which promotes AKT signaling through FZD7 and RYK, leading to increased growth and therapeutic resistance in BRAFi-resistant melanomas.
Increased MAPK reactivation in early resistance to dabrafenib/trametinib combination therapy of BRAF-mutant metastatic melanoma.
Analysis of BRAF(V600)-mutant melanoma metastases derived from 10 patients treated with the combination of dabrafenib and trametinib for resistance mechanisms and genetic correlates of response finds the functional differences between these kinases and the preponderance of MEK2 mutations in combination therapy-resistant melanomas.
Circulating tumor DNA to monitor treatment response and detect acquired resistance in patients with metastatic melanoma
The data demonstrate that ctDNA is a useful biomarker of response to kinase inhibitor therapy and can be used to monitor tumor evolution and detect the early appearance of resistance effectors.
Response of BRAF-mutant melanoma to BRAF inhibition is mediated by a network of transcriptional regulators of glycolysis.
It is shown that BRAF inhibition suppresses glycolysis via a network of transcription factors that are critical for complete BRAFi responses, and evidence is provided for the clinical potential of therapies that combine BRAFis with glyCOlysis inhibitors.
IGFBP7 Is Not Required for B-RAF-Induced Melanocyte Senescence
Circulating tumour DNA predicts response to anti-PD1 antibodies in metastatic melanoma
Longitudinal assessment of ctDNA in metastatic melanoma patients receiving treatment with PD1 inhibitors is an accurate predictor of tumour response, PFS and OS, and this may guide combination and sequencing of subsequent therapies.
Inducible but Not Constitutive Expression of PD-L1 in Human Melanoma Cells Is Dependent on Activation of NF-κB
- K. Gowrishankar, Dilini Gunatilake, S. Gallagher, Jessamy Tiffen, H. Rizos, P. Hersey
- BiologyPloS one
- 6 April 2015
Investigation of the mechanism underlying constitutive and inducible expression of programmed death receptor-1 ligand-1 in melanoma cells including cells that had acquired resistance to the BRAF inhibitor vemurafenib suggests selection of treatments that can be used in combination with monoclonal antibodies against PD1 should be considered to enhance their effectiveness and to reduce inhibitory effects melan cancer cells have against cytotoxic T cell activity.
Mechanisms and strategies to overcome resistance to molecularly targeted therapy for melanoma
The efficacy of therapies targeting the MAPK and PI3K/AKT signaling pathways in melanoma is described, the mechanisms contributing to drug resistance are detailed, and current approaches to improving outcomes further are discussed.