ArticleClinical cancer research : an official journal of the American Association for Cancer Research2010
The oncogenic BRAF kinase inhibitor PLX4032/RG7204 does not affect the viability or function of human lymphocytes across a wide range of concentrations.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers.
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Who cites it
78 citing papers in PubMed, 139 citations in OpenAlex.
- A multi-center phase II study of high dose interleukin-2 sequenced with vemurafenib in patients with BRAF-V600 mutation positive metastatic melanoma.Journal for immunotherapy of cancer · 2018Trial
- BRAF Targeting Across Solid Tumors: Molecular Aspects and Clinical Applications.International journal of molecular sciences · 2025Review
- Combination of immunotherapy and other targeted therapies in advanced cutaneous melanoma.Human vaccines & immunotherapeutics · 2022Review
- Review
- Current Status and Future Perspective of Immunotherapy in Gastrointestinal Cancers.Innovation (Cambridge (Mass.)) · 2020Review
- Current Insights into Combination Therapies with MAPK Inhibitors and Immune Checkpoint Blockade.International journal of molecular sciences · 2020Review
- Clinical Pharmacokinetic and Pharmacodynamic Considerations in the (Modern) Treatment of Melanoma.Clinical pharmacokinetics · 2019Review
- BRAF Targeting Sensitizes Resistant Melanoma to Cytotoxic T Cells.Clinical cancer research : an official journal of the American Association for Cancer Research · 2019Article
- Strategies to Improve Cancer Immune Checkpoint Inhibitors Efficacy, Other Than Abscopal Effect: A Systematic Review.Cancers · 2019Review
- Induced cross-resistance of BRAFScientific reports · 2019Article
- Combination of Immunotherapy With Targeted Therapy: Theory and Practice in Metastatic Melanoma.Frontiers in immunology · 2019Review
- Global alteration of T-lymphocyte metabolism by PD-L1 checkpoint involves a block of de novo nucleoside phosphate synthesis.Cell discovery · 2019Article
- Reversal of Resistance in Targeted Therapy of Metastatic Melanoma: Lessons Learned from Vemurafenib (BRAFCancers · 2018Review
- Changes in the TCRβ Repertoire and Tumor Immune Signature From a Cutaneous Melanoma Patient Immunized With the CSF-470 Vaccine: A Case Report.Frontiers in immunology · 2018Article
- BRAFBlood advances · 2017Article
- The combination of checkpoint immunotherapy and targeted therapy in cancer.Annals of translational medicine · 2017Review
- Overcoming resistance to targeted therapy with immunotherapy and combination therapy for metastatic melanoma.Oncotarget · 2017Review
- Immune Cell-Mediated Biodegradable Theranostic Nanoparticles for Melanoma Targeting and Drug Delivery.Small (Weinheim an der Bergstrasse, Germany) · 2017Article
- Review
- Immunomodulating property of MAPK inhibitors: from translational knowledge to clinical implementation.Laboratory investigation; a journal of technical methods and pathology · 2017Review
18 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
purposePLX4032 (RG7204), an oncogenic BRAF kinase inhibitor undergoing clinical evaluation, has high response rates in early clinical trials in patients with advanced BRAF(V600E) mutant melanoma. Combining PLX4032 with immunotherapy may allow expanding the durability of responses. The effects of PLX4032 on immune cells were studied to explore the feasibility of future combinatorial approaches with immunotherapy for melanoma. EXPERIMENTAL
designPeripheral blood mononuclear cells (PBMC) and BRAF(V600E) mutant melanoma cells were exposed to increasing concentrations of PLX4032 and the cell viability, proliferation, cell cycle, apoptosis, and phosphorylation of signaling proteins were analyzed. Effects of PLX4032 on antigen-specific T-cell function were analyzed by specific cytokine release and cytotoxicity activity.
resultsThe 50% inhibition concentration (IC(50)) of PLX4032 for resting human PBMC was between 50 and 150 μmol/L compared with an IC(50) below 1 μmol/L for sensitive BRAF(V600E) mutant melanoma cell lines. Activated lymphocytes were even more resistant with no growth inhibition up to concentrations of 250 μmol/L. PLX4032 had a marginal effect on cell-cycle arrest, apoptotic cell changes or alteration of phosphorylated signaling molecules in lymphocytes. Functional analysis of specific antigen recognition showed preserved T-cell function up to 10-μmol/L concentration of PLX4032, whereas the cytotoxic activity of PLX4032 was maintained up to high concentrations of 50 μmol/L.
conclusionsThe preserved viability and function of lymphocytes exposed to high concentrations of PLX4032 suggest that this agent could be a potential candidate for combining with immunotherapy strategies for the treatment of patients with BRAF(V600)(E) mutant melanoma.
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Registered trials
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.