ArticleOncoimmunology2016
Combined treatment with dabrafenib and trametinib with immune-stimulating antibodies for BRAF mutant melanoma.
Article in Oncoimmunology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
57 citing papers in PubMed, 98 citations in OpenAlex.
- COMBI-I: Long-Term Overall Survival With Spartalizumab Plus Dabrafenib and Trametinib inJournal of clinical oncology : official journal of the American Society of Clinical Oncology · 2026Trial
- Dabrafenib, trametinib and pembrolizumab or placebo in BRAF-mutant melanoma.Nature medicine · 2019Trial
- Article
- Neoantigen Targeting as a Novel Approach for Therapy-Resistant Tumors.Molecular diagnosis & therapy · 2026Review
- Multi-tyrosine kinase inhibitors: exploring immunomodulatory effects on various immune cell types in cancer.Cancer cell international · 2026Review
- Advancing Cancer Treatment: A Review of Immune Checkpoint Inhibitors and Combination Strategies.Cancers · 2025Review
- Strategies to enhance the therapeutic efficacy of anti-PD-1 antibody, anti-PD-L1 antibody and anti-CTLA-4 antibody in cancer therapy.Journal of translational medicine · 2024Review
- The role of CRAF in cancer progression: from molecular mechanisms to precision therapies.Nature reviews. Cancer · 2024Review
- Combination of immune-checkpoint inhibitors and targeted therapies for melanoma therapy: The more, the better?Cancer metastasis reviews · 2023Review
- MEK inhibition enhances presentation of targetable MHC-I tumor antigens in mutant melanomas.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- The future of targeted kinase inhibitors in melanoma.Pharmacology & therapeutics · 2022Review
- Immune Checkpoint Inhibitors and RAS-ERK Pathway-Targeted Drugs as Combined Therapy for the Treatment of Melanoma.Biomolecules · 2022Review
- Gut Microbiota and Therapy in Metastatic Melanoma: Focus on MAPK Pathway Inhibition.International journal of molecular sciences · 2022Review
- Article
- Advanced Acral Melanoma Therapies: Current Status and Future Directions.Current treatment options in oncology · 2022Review
- Triplet Therapy in Melanoma - Combined BRAF/MEK Inhibitors and Anti-PD-(L)1 Antibodies.Current oncology reports · 2022Review
- Immunomodulatory Properties of PI3K/AKT/mTOR and MAPK/MEK/ERK Inhibition Augment Response to Immune Checkpoint Blockade in Melanoma and Triple-Negative Breast Cancer.International journal of molecular sciences · 2022Review
- Overcoming differential tumor penetration of BRAF inhibitors using computationally guided combination therapy.Science advances · 2022Article
- Stromal Factors as a Target for Immunotherapy in Melanoma and Non-Melanoma Skin Cancers.International journal of molecular sciences · 2022Review
- MEK1/2 inhibition transiently alters the tumor immune microenvironment to enhance immunotherapy efficacy against head and neck cancer.Journal for immunotherapy of cancer · 2022Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
The combination of targeted therapy with BRAF and MEK inhibitors has become the standard of care in patients with BRAF (V600E) mutant melanoma, but responses are not durable. In addition, the impressive clinical benefits with anti-PD-1 and anti-PD-L1 antibodies (Ab) in patients with heavily pretreated metastatic melanoma and the synergistic effect of dabrafenib, trametinib and anti-PD-1 compared with single therapy alone groups support the idea that combining dabrafenib, trametinib and immunotherapy based on PD-1 blockade could be an interesting approach in the treatment of metastatic melanoma. With our mouse model of syngeneic BRAF (V600E) driven melanoma (SM1), we tested whether the addition of an immunostimulatory Ab targeting CD137 (4-1BB) and/or CD134 (OX40) would enhance the antitumor effect of dabrafenib, trametinib and anti-PD-1 or anti-PD-L1 therapy. In vitro studies showed that the combination group of dabrafenib, trametinib and anti-PD-1 increases CD8(+) tumor infiltrating lymphocytes (TILs), as well as CD4(+) T cells and tumor-associated macrophages (TAMs). An upregulation of PD-L1 was observed in the combination of dabrafenib, trametinib and anti-PD-1 therapy. Combination of dabrafenib, trametinib and anti-PD-1, with either anti-CD137 or anti-CD134, showed a superior antitumor effect, but the five-agent combination was not superior to the four-agent combinations. In conclusion, the combination of dabrafenib, trametinib, anti-PD1 or anti-PD-L1 therapy results in robust antitumor activity, which is further improved by adding the immune-stimulating Ab anti-CD137 or anti-CD134. Our findings support the testing of these combinations in patients with BRAF (V600E) mutant metastatic 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.