ArticleEMBO molecular medicine2018
Co-targeting BET and MEK as salvage therapy for MAPK and checkpoint inhibitor-resistant melanoma.
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Article in EMBO molecular medicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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55citing papers in PubMed
4.7field-weighted citation impact, top 4% of its field
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55 citing papers in PubMed, 92 citations in OpenAlex.
- BRD2 upregulation as a pan-cancer adaptive resistance mechanism to BET inhibition.Cellular & molecular biology letters · 2026Article
- Emerging Role of Transcription Factor 19 (TCF19) in Inflammatory Disease and Cancer.Biomolecules · 2026Review
- Melanoma: Pathogenesis and Targeted Therapy.MedComm · 2026Review
- TCF19 promotes gastric cancer progression through MCM6.BMC gastroenterology · 2025Article
- BET proteins mediate survival mechanisms in human schwannoma model cells challenged with trametinib but not brigatinib.Oncogene · 2025Article
- A methyl-to-acetyl switch in H3K27 drives metabolic reprogramming and resistance to BRAFNeoplasia (New York, N.Y.) · 2025Article
- BRD2 Upregulation as a Pan-Cancer Adaptive Resistance Mechanism to BET Inhibition.bioRxiv : the preprint server for biology · 2025Article
- Selective abrogation of S6K2 identifies lipid homeostasis as a survival vulnerability in MAPK inhibitor-resistantScience translational medicine · 2025Article
- Bromodomain inhibition targeting BPTF in the treatment of melanoma and other solid tumors.Clinical & experimental metastasis · 2024Review
- Unique vulnerability of RAC1-mutant melanoma to combined inhibition of CDK9 and immune checkpoints.Oncogene · 2024Article
- Exploring the In Vitro and In Vivo Therapeutic Potential of BRAF and MEK Inhibitor Combination in NRAS-Mutated Melanoma.Cancers · 2023Article
- Bromodomain and extraterminal (BET) proteins: biological functions, diseases, and targeted therapy.Signal transduction and targeted therapy · 2023Review
- The OSUMMER lines: A series of ultraviolet-accelerated NRAS-mutant mouse melanoma cell lines syngeneic to C57BL/6.Pigment cell & melanoma research · 2023Article
- BET inhibitors synergize with sunitinib in melanoma through GDF15 suppression.Experimental & molecular medicine · 2023Article
- New Insights into the Phenotype Switching of Melanoma.Cancers · 2022Review
- Epigenetic Mechanisms Underlying Melanoma Resistance to Immune and Targeted Therapies.Cancers · 2022Review
- Current understanding of epigenetics role in melanoma treatment and resistance.Cancer cell international · 2022Review
- Phase Ib Study of the BET Inhibitor GS-5829 as Monotherapy and Combined with Enzalutamide in Patients with Metastatic Castration-Resistant Prostate Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022Article
- Review
- Bromodomain inhibition overcomes treatment resistance in distinct molecular subtypes of melanoma.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
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Authors and funding
29 authors at 7 institutions in 1 country.
Ileabett M Echevarría-VargasMolecular & Cellular Oncogenesis Program, The Wistar Institute, Philadelphia, PA, USA.
Patricia I Reyes-UribeMolecular & Cellular Oncogenesis Program, The Wistar Institute, Philadelphia, PA, USA.
Adam N GuterresMolecular & Cellular Oncogenesis Program, The Wistar Institute, Philadelphia, PA, USA.
Xiangfan YinMolecular & Cellular Oncogenesis Program, The Wistar Institute, Philadelphia, PA, USA.
Andrew V KossenkovMolecular & Cellular Oncogenesis Program, The Wistar Institute, Philadelphia, PA, USA.
Qin LiuMolecular & Cellular Oncogenesis Program, The Wistar Institute, Philadelphia, PA, USA.
Gao ZhangMolecular & Cellular Oncogenesis Program, The Wistar Institute, Philadelphia, PA, USA.
Clemens KreplerMolecular & Cellular Oncogenesis Program, The Wistar Institute, Philadelphia, PA, USA.
Chaoran ChengCollege of Computing Sciences, New Jersey Institute of Technology, Newark, NJ, USA.
Zhi WeiCollege of Computing Sciences, New Jersey Institute of Technology, Newark, NJ, USA.
Rajasekharan SomasundaramMolecular & Cellular Oncogenesis Program, The Wistar Institute, Philadelphia, PA, USA.
Giorgos KarakousisAbramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA.
Wei XuAbramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA.
Jennifer Jd MorrissetteCenter for Personalized Diagnostics, Hospital of the University of Pennsylvania University of Pennsylvania, Philadelphia, PA, USA.
Yiling LuDepartment of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Gordon B MillsDepartment of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Ryan J SullivanMassachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA.
Miao BenchunMassachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA.
Dennie T FrederickMassachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA.
Genevieve BolandDepartment of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Keith T FlahertyMassachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA.
Ashani T WeeraratnaMelanoma Research Center, The Wistar Institute, Philadelphia, PA, USA.
Meenhard HerlynMolecular & Cellular Oncogenesis Program, The Wistar Institute, Philadelphia, PA, USA.
Ravi AmaravadiDepartment of Surgery, Hospital of the University of Pennsylvania, Philadelphia, PA, USA.
Lynn M SchuchterDepartment of Surgery, Hospital of the University of Pennsylvania, Philadelphia, PA, USA.
Christin E BurdDepartments of Molecular Genetics and Cancer Biology and Genetics, Ohio State University, Columbus, OH, USA.
Andrew E AplinDepartment of Cancer Biology and Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, USA.
Xiaowei XuDepartment of Surgery, Hospital of the University of Pennsylvania, Philadelphia, PA, USA.
Jessie VillanuevaMolecular & Cellular Oncogenesis Program, The Wistar Institute, Philadelphia, PA, USA jvillanueva@wistar.org.ORCID 0000-0001-5701-2609
The Wistar Institute · USHarvard University · USHospital of the University of Pennsylvania · USThe University of Texas MD Anderson Cancer Center · USNew Jersey Institute of Technology · USThomas Jefferson University · USUniversity of Pennsylvania · US
Funding
Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Fabien Delerue · 1985 to 2026
$290.8MUNIVERSITY OF PENNSYLVANIA CAN CTR SUPPORT GRANTP30CA016520 · NCI · UNIVERSITY OF PENNSYLVANIA · PI Robert H. Vonderheide · 1985 to 2026
$222.3MTranslational Therapeutics Research Program (TT)P30CA016058 · NCI · OHIO STATE UNIVERSITY · PI Jennifer A. Woyach · 1985 to 2026
$132.3MTumor Microenvironment and MetastasisP30CA010815 · NCI · WISTAR INSTITUTE · PI Luis J Montaner · 1985 to 2026
$75.9MTargeting the MAP and PI3 Kinase Pathways in MelanomaP01CA114046 · NCI · WISTAR INSTITUTE · PI HERLYN, MEENHARD F, WEERARATNA, ASHANI T · 2008 to 2023
$37.1MTRAINING PROGRAM IN BASIC CANCER RESEARCHT32CA009171 · NCI · WISTAR INSTITUTE · PI Alessandro Gardini · 1985 to 2026
$15.3MTargeted Combination Therapy for MelanomaP50CA174523 · NCI · WISTAR INSTITUTE · PI HERLYN, MEENHARD F · 2014 to 2018
$11.1MTargeting TERT in MelanomaR01CA215733 · NCI · WISTAR INSTITUTE · PI VILLANUEVA, JESSIE · 2017 to 2021
$2.4MIntegrative Approach to Comprehensive Analysis of High Throughput Data on a Cancer Center LevelR50CA211199 · NCI · WISTAR INSTITUTE · PI Andrew V Kossenkov · 2016 to 2026
$1.6MMolecular approaches to overcome intrinsic drug resistance in BRAF and NRAS-mutanK01CA175269 · NCI · WISTAR INSTITUTE · PI VILLANUEVA, JESSIE · 2013 to 2017
$754kFunctional Proteomics by Reverse Phase Protein Array in CancerR50CA221675 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI LU, YILING · 2017 to 2021
$726kPurchase of a Q Exactive HF mass spectrometer system for metabolomicsS10OD023586 · OD · WISTAR INSTITUTE · PI SPEICHER, DAVID W. · 2017 to 2017
$600kNCI NIH HHS K01 CA175269NCI NIH HHS P01 CA114046NCI NIH HHS P30 CA010815NCI NIH HHS P30 CA016058NCI NIH HHS P30 CA016520NCI NIH HHS P30 CA016672NCI NIH HHS P50 CA174523NCI NIH HHS R01 CA215733NCI NIH HHS R50 CA211199NCI NIH HHS R50 CA221675NCI NIH HHS T32 CA009171NIH HHS S10 OD023586
Abstract
Despite novel therapies for melanoma, drug resistance remains a significant hurdle to achieving optimal responses. NRAS-mutant melanoma is an archetype of therapeutic challenges in the field, which we used to test drug combinations to avert drug resistance. We show that BET proteins are overexpressed in NRAS-mutant melanoma and that high levels of the BET family member BRD4 are associated with poor patient survival. Combining BET and MEK inhibitors synergistically curbed the growth of
Indexed as
Xenograft Model Antitumor AssaysAcetanilidesAnimalsBromodomain Containing ProteinsCell Cycle ProteinsCell Line, TumorDrug Resistance, NeoplasmGene Expression ProfilingHeterocyclic Compounds, 3-RingHumansMAP Kinase Kinase 1MAP Kinase Signaling SystemMelanomaMice, Inbred C57BLMice, Inbred NODMice, KnockoutAcetanilidesBRD4 protein, humanbromodomain and extra-terminal domain protein, humanBromodomain Containing ProteinsCell Cycle ProteinsHeterocyclic Compounds, 3-RingMAP Kinase Kinase 1Nuclear ProteinsOTX015Protein Kinase InhibitorsProteinsTranscription FactorsBETcombination therapydrug resistancemelanomamutant NRAS
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