Evidence map›Paper›PMID 41776501›Full record

ArticleMolecular cancer2026

Clonal dynamics shaped by diverse drug-tolerant persister states in melanoma resistance.

Haiyin Li, Yeqing Chen, Jessica Kaster, Maggie Dunne, Min Xiao, Ling Li, Monzy Thomas, Nazifa Promi, Dylan Fingerman, Gregory Schuyler Brown and 23 more

Abstract read
In one paragraph

Article in Molecular cancer, 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. TFAP2A links drug resistance to antitumor immunity.bioRxiv : the preprint server for biology · 2026
    Article
  2. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

33 authors.

Haiyin LiThe Wistar Institute, Philadelphia, PA, USA.
Yeqing ChenThe Wistar Institute, Philadelphia, PA, USA.
Jessica KasterThe Wistar Institute, Philadelphia, PA, USA.
Maggie DunneThe Wistar Institute, Philadelphia, PA, USA.
Min XiaoThe Wistar Institute, Philadelphia, PA, USA.
Ling LiThe Wistar Institute, Philadelphia, PA, USA.
Monzy ThomasThe Wistar Institute, Philadelphia, PA, USA.
Nazifa PromiThe Wistar Institute, Philadelphia, PA, USA.
Dylan FingermanThe Wistar Institute, Philadelphia, PA, USA.
Gregory Schuyler BrownThe Wistar Institute, Philadelphia, PA, USA.
Qiuxian ZhengThe Wistar Institute, Philadelphia, PA, USA.
Xingyue ZhuThe Wistar Institute, Philadelphia, PA, USA.
McKenna RealeThe Wistar Institute, Philadelphia, PA, USA.
Andrew PattersonThe Wistar Institute, Philadelphia, PA, USA.
Le GaoDepartment of Computer Science, New Jersey Institute of Technology, Newark, NJ, USA.
Xuxiang ZhangDepartment of Computer Science, New Jersey Institute of Technology, Newark, NJ, USA.
Siqi JiangDepartment of Computer Science, New Jersey Institute of Technology, Newark, NJ, USA.
Tianxing HuDepartment of Computer Science, New Jersey Institute of Technology, Newark, NJ, USA.
Hanzhang FangDepartment of Computer Science, New Jersey Institute of Technology, Newark, NJ, USA.
Jianlan RenDepartment of Computer Science, New Jersey Institute of Technology, Newark, NJ, USA.
Cong QiDepartment of Computer Science, New Jersey Institute of Technology, Newark, NJ, USA.
Luyang WangThe Wistar Institute, Philadelphia, PA, USA.
Haiwei MouThe Wistar Institute, Philadelphia, PA, USA.
Gatha ThackerThe Wistar Institute, Philadelphia, PA, USA.
Eric Ramirez SalazarThe Wistar Institute, Philadelphia, PA, USA.
Jessie VillanuevaThe Wistar Institute, Philadelphia, PA, USA.
Arjun RajDepartment of Bioengineering, School of Engineering and Applied Sciences, University of Pennsylvania, Philadelphia, PA, USA.
Dave Sb HoonSt John's Cancer Institute, Santa Monica, CA, USA.
Tian BinThe Wistar Institute, Philadelphia, PA, USA.
Jozef MadzoThe Wistar Institute, Philadelphia, PA, USA.
Zhi WeiDepartment of Computer Science, New Jersey Institute of Technology, Newark, NJ, USA.
Noam AuslanderThe Wistar Institute, Philadelphia, PA, USA.
Meenhard HerlynThe Wistar Institute, Philadelphia, PA, USA. herlynm@wistar.org.

Funding

TRAINING PROGRAM IN BASIC CANCER RESEARCHT32CA009171 · NCI · WISTAR INSTITUTE · PI Alessandro Gardini · 1985 to 2026
$15.3M
Research Project 2 - Targeting Melanoma Tumor Survival and Apoptotic MachineryU54CA224070 · NCI · WISTAR INSTITUTE · PI Meenhard F Herlyn · 2017 to 2026
$13.9M
Regulation of gene expression by alternative polyadenylationR35GM153277 · NIGMS · WISTAR INSTITUTE · PI BIN TIAN · 2024 to 2026
$2.0M
Regulation and Functions of 3'UTRs in Cellular StressR01GM129069 · NIGMS · WISTAR INSTITUTE · PI TIAN, BIN · 2018 to 2021
$1.5M
NCI NIH HHS T32 CA009171NCI NIH HHS U54 CA224070NIGMS NIH HHS R01 GM129069NIGMS NIH HHS R35 GM153277NIH/NCI grants P01 CA114046-15, R01 CA238237-05, R01 CA240362-05, R01 CA241148-05, P50 CA261608-03, U54 CA224070-05Sheldon G. Adelson Medical Research Grant R-202206-00540
6 · The paper itself

Abstract

backgroundMost advanced melanomas initially respond to targeted therapy but eventually relapse. Increasing evidence suggests that drug-tolerant persister cells can adopt a reversible drug-refractory state and represent a key driver of therapeutic resistance.

methodsWe developed MeRLin, a lineage tracing platform that integrates cellular barcoding, single-cell transcriptomic profiling, RNA fluorescence in situ hybridization, and computational analyses to track clonal and transcriptional dynamics in a patient-derived melanoma model during prolonged targeted therapy. Longitudinal analyses enabled the characterization of clonal fates, transcriptional states, and spatial organization of persister populations.

resultsClonal dynamics showed that persister subpopulations initially responded to therapy, persisted through minimal residual disease, and expanded during tumor recurrence. Four persister-associated transcriptional states characterized by stress-like, lipid metabolism, PI3K signaling, and extracellular matrix remodeling programs were associated with persister populations arising from minor pre-treatment subpopulations under sustained drug pressure. Spatial transcriptomic analyses revealed structured spatial organization of these programs and suggested coordinated autocrine and paracrine interactions among persister states. Targeted barcode RNA fluorescence in situ hybridization enabled spatial mapping of clonal identity and gene expression, revealing in situ co-localization of a dominant resistant clone marked by SLC2A1 expression.

conclusionsTogether, MeRLin provides a robust framework for dissecting cancer heterogeneity and characterizing persister subpopulations. Our findings demonstrate that melanoma recurrence is associated with diverse, spatially organized persister states linked to adaptive transcriptional programs.

Indexed as

Clonal EvolutionDrug Resistance, NeoplasmMelanomaAntineoplastic AgentsGene Expression ProfilingGene Expression Regulation, NeoplasticHumansSingle-Cell Gene Expression AnalysisAntineoplastic AgentsCancer plasticityClonal dynamicsDrug-tolerant persister cellsLineage tracingMelanoma therapy resistanceSingle-cell transcriptomicsSpatial transcriptomicsTumor heterogeneity

Identifiers

PMID41776501
PMCPMC13162433

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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.