Evidence map›Paper›PMID 42362544›Full record

ArticleNature communications2026

Personalized targeting of BCL2 family proteins overcomes acquired resistance to BRAF-MEK inhibitors in preclinical melanoma.

Y N Vashisht Gopal, Evelyn de Groot, Kaley Loftin, Barbara Knighton, Debora Ledesma, Courtney Hudgens, Diana Shamsutdinova, Mehboob Ali, Zhenlin Ju, Min Xiao and 15 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

25 authors.

Y N Vashisht GopalDepartment of Melanoma Medical Oncology, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA. vynanda@mdanderson.org.ORCID http://orcid.org/0000-0002-3118-0011
Evelyn de GrootDepartment of Melanoma Medical Oncology, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.
Kaley LoftinDepartment of Melanoma Medical Oncology, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.
Barbara KnightonDepartment of Melanoma Medical Oncology, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.
Debora LedesmaDept of Translational Molecular Pathology, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.ORCID http://orcid.org/0000-0002-6670-7645
Courtney HudgensDept of Translational Molecular Pathology, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.ORCID http://orcid.org/0000-0001-8312-7485
Diana ShamsutdinovaDept of Translational Molecular Pathology, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.
Mehboob AliDepartment of Melanoma Medical Oncology, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.
Zhenlin JuDept of Bioinformatics and Computational Biology, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.
Min XiaoEllen and Ronald Caplan Cancer Center, Wistar Institute, Philadelphia, PA, USA.
Toshitha KannanEllen and Ronald Caplan Cancer Center, Wistar Institute, Philadelphia, PA, USA.ORCID http://orcid.org/0009-0007-7775-6585
Gregory FontenotInstitute of Biosciences and Technology, Texas A&M University, Houston, TX, USA.
Michael S NakazawaDept of Sarcoma Medical Oncology, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.ORCID http://orcid.org/0000-0002-6272-5467
Monzy ThomasEllen and Ronald Caplan Cancer Center, Wistar Institute, Philadelphia, PA, USA.
Khalida WaniDept of Translational Molecular Pathology, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.
Clifford StephanInstitute of Biosciences and Technology, Texas A&M University, Houston, TX, USA.ORCID http://orcid.org/0000-0003-0657-6484
Phyu P AungDept of Anatomic Pathology, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.ORCID http://orcid.org/0000-0002-3398-0573
Lawrence N KwongDept of Translational Molecular Pathology, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.ORCID http://orcid.org/0000-0001-8370-1432
Janos RoszikDepartment of Melanoma Medical Oncology, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.
Rehan AkbaniDept of Bioinformatics and Computational Biology, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.ORCID http://orcid.org/0000-0003-2686-7721
Andrew KossenkovEllen and Ronald Caplan Cancer Center, Wistar Institute, Philadelphia, PA, USA.
Vito W RebeccaJohns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.ORCID http://orcid.org/0000-0001-8124-0900
Ryan J SullivanCutaneous Medical Oncology Program, Mass General Brigham Cancer Institute and Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0001-5344-6645
Meenhard HerlynEllen and Ronald Caplan Cancer Center, Wistar Institute, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0003-0839-0739
Michael A DaviesDepartment of Melanoma Medical Oncology, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.ORCID http://orcid.org/0000-0002-0977-0912

Funding

Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI DIANE BODURKA · 1985 to 2026
$290.8M
Research Project 2 - Targeting Melanoma Tumor Survival and Apoptotic MachineryU54CA224070 · NCI · WISTAR INSTITUTE · PI Meenhard F Herlyn · 2017 to 2026
$13.9M
The University of Texas MD Anderson Cancer Center SPORE in MelanomaP50CA221703 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI WARGO, JENNIFER A. · 2019 to 2023
$10.3M
NCI NIH HHS P30 CA016672NCI NIH HHS P50 CA221703NCI NIH HHS U54 CA224070U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) CA224070
6 · The paper itself

Abstract

There are currently no effective targeted therapies for BRAF-mutant metastatic melanoma patients with acquired resistance to approved BRAF and MEK inhibitors (BRAFi and MEKi), and very few ongoing clinical trials. Anti-apoptotic BCL2 family proteins promote de novo resistance to several therapies, including single-agent BRAFi in BRAF-mutant melanomas. In this study, in vivo testing of a large collection of patient-derived xenograft (PDX) models from melanoma patients with acquired resistance to BRAFi or BRAFi+MEKi shows that combining BCL2 inhibitors (BCL2i; navitoclax or venetoclax) with BRAFi+MEKi induces tumor regressions in a subset of these PDXs. High basal BCL2 predicts response whereas high basal MCL1 predicts resistance to this strategy. MCL1 overexpression studies functionally validate its role in resistance. Further, combining BRAFi+MEKi with an MCL1 inhibitor (MCL1i) counteracts resistance and interestingly decreases MCL1i-associated markers of cardiotoxicity. Together these studies identify potential personalized strategies to improve outcomes in this challenging patient population.

Indexed as

Drug Resistance, NeoplasmMelanomaProtein Kinase InhibitorsProto-Oncogene Proteins B-rafProto-Oncogene Proteins c-bcl-2Aniline CompoundsAnimalsBridged Bicyclo Compounds, HeterocyclicCell Line, TumorFemaleHumansMiceMyeloid Cell Leukemia Sequence 1 ProteinPrecision MedicineSulfonamidesXenograft Model Antitumor AssaysAniline CompoundsBCL2 protein, humanBRAF protein, humanBridged Bicyclo Compounds, HeterocyclicMCL1 protein, humanMyeloid Cell Leukemia Sequence 1 ProteinnavitoclaxProtein Kinase InhibitorsProto-Oncogene Proteins B-rafProto-Oncogene Proteins c-bcl-2Sulfonamidesvenetoclax

Identifiers

PMID42362544
PMCPMC13421458

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

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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.