Evidence mapPaperPMID 41807883Full record

ReviewMolecular biomedicine2026

BRAF inhibitor resistance in melanoma: from resistance mechanisms to therapeutic innovations.

Yan Shang, Tingping Cao, Junyan Li, Juan Li, Lingnan Zhang, Qiqi Ma, Lanyan Feng, Hailong Zhao

Abstract readReview
In one paragraph

Review in Molecular biomedicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Article
  2. Elucidating the Nexus of Mitochondrial Dysfunction and Oncometabolite Accumulation in Tumorigenesis.Nigerian medical journal : journal of the Nigeria Medical Association
    Review
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

8 authors.

Yan ShangDepartment of Pathophysiology, School of Preclinical Medicine, Zunyi Medical University, Zunyi Guizhou, 563003, China.
Tingping CaoDepartment of Pathophysiology, School of Preclinical Medicine, Zunyi Medical University, Zunyi Guizhou, 563003, China.
Junyan LiDepartment of Medical Genetics, School of Preclinical Medicine, Zunyi Medical University, Zunyi Guizhou, 563003, China.
Juan LiDepartment of Pathophysiology, School of Preclinical Medicine, Zunyi Medical University, Zunyi Guizhou, 563003, China.
Lingnan ZhangKey Laboratory of Basic Pharmacology of Ministry of Education, Zunyi Medical University, Zunyi Guizhou, 563003, China.
Qiqi MaDepartment of Pathophysiology, School of Preclinical Medicine, Zunyi Medical University, Zunyi Guizhou, 563003, China.
Lanyan FengDepartment of Pathophysiology, School of Preclinical Medicine, Zunyi Medical University, Zunyi Guizhou, 563003, China.
Hailong ZhaoDepartment of Pathophysiology, School of Preclinical Medicine, Zunyi Medical University, Zunyi Guizhou, 563003, China. hailongzhao@zmu.edu.cn.

Funding

National College Students Innovation and Entrepreneurship Training Program S202310661167National College Students Innovation and Entrepreneurship Training Program S202310661178National College Students Innovation and Entrepreneurship Training Program S2024106612300the Guizhou Province Science and Technology Plan Project QKHJC [2019] 1334the Guizhou Province Science and Technology Plan Project QKHJC -ZK [2022] General 622the National Natural Science Foundation of China Regional Project 82060503
6 · The paper itself

Abstract

BRAF inhibitors (BRAFi) have transformed the treatment of BRAF mutant melanoma, but inherent and acquired resistance remains a major barrier to curative outcomes. Resistance arises from interconnected mechanisms: genetic alterations reactivating the MAPK pathway or bypass cascades (e.g., PI3K/AKT/RTK), epigenetic modulation, metabolic reprogramming, and the tumor microenvironment (TME) remodeling. Despite extensive research into these mechanisms, a cohesive framework linking each resistance module to targeted therapeutic strategies is lacking. This review systematically categorizes resistance into intrinsic and acquired subtypes: intrinsic resistance is driven by constitutive molecular traits of BRAF mutant melanoma (e.g., persistent MAPK activation, baseline PI3K/AKT hyperactivity), while acquired resistance emerges via therapeutic pressure-induced genetic mutations, epigenetic shifts, metabolic reprogramming, or TME modifications. For each identified resistance mechanism, we provide a detailed examination of corresponding therapeutic advancements. These encompass the development of next-generation BRAFi, strategically designed combination therapies, epigenetic modulators, immunotherapeutic approaches, and RNA-based therapeutic agents. Furthermore, we underscore the pivotal role of state-of-the-art technologies, such as liquid biopsies, single-cell multi-omics analyses, and artificial intelligence, in facilitating precise resistance monitoring and personalized therapy selection. By integrating these insights, we present a structured, translationally focused framework to guide basic research and clinical decision-making, ultimately advancing precision salvage therapy and trials aimed at preventing or overcoming BRAFi resistance.

Indexed as

Drug Resistance, NeoplasmMelanomaProtein Kinase InhibitorsProto-Oncogene Proteins B-rafAnimalsAntineoplastic AgentsEpigenesis, GeneticHumansMolecular Targeted TherapyMutationTumor MicroenvironmentAntineoplastic AgentsBRAF protein, humanProtein Kinase InhibitorsProto-Oncogene Proteins B-rafBRAF inhibitorDrug resistanceMelanomaPrecision medicineTargeted therapy

Identifiers

PMID41807883
PMCPMC12976322

What Socratic holds

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LicenceCC BY
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Registered trials

None linked

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 Socratic graph.