Evidence map›Paper›PMID 42624103›Full record

ArticleMed (New York, N.Y.)2026

Melanoma to rhabdomyosarcoma plasticity in the setting of immunotherapy.

Andrew D Knight, Emily J Robitschek, Jia-Ren Lin, Tyler Aprati, Giuseppe Tarantino, Jaijia Chen, Dennie T Frederick, Alvin Shi, Ana B Larque, Benchun Miao and 12 more

Abstract readCase Reports
PubMed Publisher
In one paragraph

Article in Med (New York, N.Y.), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

22 authors.

Andrew D KnightDepartment of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Krantz Family Center for Cancer Research, Massachusetts General Hospital Cancer Center, Boston, MA, USA.
Emily J RobitschekDepartment of Medical Oncology, Dana Farber Cancer Institute, Boston, MA, USA.
Jia-Ren LinHarvard Ludwig Center and Laboratory of Systems Pharmacology, Harvard Medical School, Boston, MA, USA.
Tyler ApratiDepartment of Medical Oncology, Dana Farber Cancer Institute, Boston, MA, USA.
Giuseppe TarantinoDepartment of Medical Oncology, Dana Farber Cancer Institute, Boston, MA, USA.
Jaijia ChenDepartment of Medical Oncology, Dana Farber Cancer Institute, Boston, MA, USA.
Dennie T FrederickDepartment of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Krantz Family Center for Cancer Research, Massachusetts General Hospital Cancer Center, Boston, MA, USA.
Alvin ShiMassachusetts Institute of Technology, Cambridge, MA, USA.
Ana B LarqueDepartment of Pathology, University of Barcelona, Barcelona, Spain.
Benchun MiaoKrantz Family Center for Cancer Research, Massachusetts General Hospital Cancer Center, Boston, MA, USA; Department of Surgical Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Rumya S RaghavanKrantz Family Center for Cancer Research, Massachusetts General Hospital Cancer Center, Boston, MA, USA; Department of Surgical Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Tatyana SharovaKrantz Family Center for Cancer Research, Massachusetts General Hospital Cancer Center, Boston, MA, USA; Department of Surgical Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
John H ShinDepartment of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Peter SorgerHarvard Ludwig Center and Laboratory of Systems Pharmacology, Harvard Medical School, Boston, MA, USA.
Manolis KellisHarvard Ludwig Center and Laboratory of Systems Pharmacology, Harvard Medical School, Boston, MA, USA.
Keith T FlahertyDepartment of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Krantz Family Center for Cancer Research, Massachusetts General Hospital Cancer Center, Boston, MA, USA.
Nir HacohenKrantz Family Center for Cancer Research, Massachusetts General Hospital Cancer Center, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Genevieve M BolandKrantz Family Center for Cancer Research, Massachusetts General Hospital Cancer Center, Boston, MA, USA; Department of Surgical Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Ivan ChebibDepartment of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
David LiuDepartment of Medical Oncology, Dana Farber Cancer Institute, Boston, MA, USA. Electronic address: david_liu@dfci.harvard.edu.
Ryan J SullivanDepartment of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Krantz Family Center for Cancer Research, Massachusetts General Hospital Cancer Center, Boston, MA, USA. Electronic address: rsullivan7@mgh.harvard.edu.
Arnav MehtaDepartment of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Krantz Family Center for Cancer Research, Massachusetts General Hospital Cancer Center, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA. Electronic address: amehta@broadinstitute.org.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundAcquired resistance to immune checkpoint inhibitors (ICIs) remains a significant challenge in the treatment of metastatic melanoma. Phenotypic plasticity, such as dedifferentiation and transdifferentiation, is an increasingly recognized mechanism of treatment resistance.

methodsWe present a case of a 70-year-old man with metastatic melanoma who experienced progression through sequential treatments including pembrolizumab in combination with the HDAC inhibitor entinostat and ipilimumab. During treatment, a histologically distinct pleomorphic rhabdomyosarcoma (RMS) emerged at metastatic sites. Longitudinally acquired tumor samples representing both phenotypes were analyzed using whole-exome sequencing (WES), RNA sequencing (RNA-seq), and high-plex tissue imaging (spatial proteomics).

findingsWES revealed driver mutations (e.g., NRAS and NF1) and loss of heterozygosity (LOH) shared between phenotypes indicating a common ancestral clone. Phylogenetic analysis demonstrated an early divergence of the phenotypes, with each later acquiring unique mutations. RNA-seq showed mutually exclusive expression of lineage-specific markers as well as epithelial-mesenchymal transition and myogenic gene set enrichment in the RMS samples. High-plex imaging identified distinct tumor microenvironments, with RMS lesions enriched in CD163

conclusionsThis case provides molecular evidence of phenotypic plasticity occurring under the selective pressure of immune checkpoint inhibitor therapy.

fundingThis study was supported by the National Institutes of Health (K12CA087723 and K08CA234458), the Doris Duke Charitable Foundation, and Adelson Medical Research Foundation.

Indexed as

MelanomaRhabdomyosarcomaAgedAntibodies, Monoclonal, HumanizedDrug Resistance, NeoplasmExome SequencingHumansImmune Checkpoint InhibitorsImmunotherapyIpilimumabMaleMutationTumor MicroenvironmentAntibodies, Monoclonal, HumanizedImmune Checkpoint InhibitorsIpilimumabpembrolizumabclonal evolutionepigenetic reprogrammingimmune checkpoint inhibitorslineage plasticitymelanomarhabdomyosarcomatranscriptional reprogrammingTranslation to patientstumor evolution

Identifiers

PMID42624103

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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.