Evidence map›Paper›PMID 40473796›Full record

ArticleCommunications medicine2025

Suppression of NRAS-mutant melanoma growth with NRAS-targeting Antisense Oligonucleotide treatment reveals therapeutically relevant kinase co-dependencies.

Valentin Feichtenschlager, Yixuan James Zheng, Tiange Qu, Dasha Hohlova, Ciara Callanan, Linan Chen, Christopher Chen, Wilson Ho, Albert Lee, Yeonjoo Hwang and 7 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Communications medicine, 2025. 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. 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

17 authors.

Valentin FeichtenschlagerDepartment of Dermatology, Mt Zion Cancer Research Center, University of California San Francisco, San Francisco, CA, USA. valentin.feichtenschlager@hotmail.com.ORCID http://orcid.org/0000-0002-3263-9285
Yixuan James ZhengDepartment of Dermatology, Mt Zion Cancer Research Center, University of California San Francisco, San Francisco, CA, USA.
Tiange QuDepartment of Orofacial Science, Health Science West, University of California San Francisco School of Dentistry, San Francisco, CA, USA.
Dasha HohlovaDepartment of Dermatology, Mt Zion Cancer Research Center, University of California San Francisco, San Francisco, CA, USA.
Ciara CallananDepartment of Dermatology, Mt Zion Cancer Research Center, University of California San Francisco, San Francisco, CA, USA.
Linan ChenDepartment of Dermatology, Mt Zion Cancer Research Center, University of California San Francisco, San Francisco, CA, USA.
Christopher ChenDepartment of Dermatology, Mt Zion Cancer Research Center, University of California San Francisco, San Francisco, CA, USA.
Wilson HoDepartment of Dermatology, Mt Zion Cancer Research Center, University of California San Francisco, San Francisco, CA, USA.
Albert LeeDepartment of Dermatology, Mt Zion Cancer Research Center, University of California San Francisco, San Francisco, CA, USA.
Yeonjoo HwangDepartment of Hematology-Oncology, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0002-3000-4710
Arowyn CourtrightDepartment of Dermatology, Mt Zion Cancer Research Center, University of California San Francisco, San Francisco, CA, USA.
Thy NguyenDepartment of Dermatology, Mt Zion Cancer Research Center, University of California San Francisco, San Francisco, CA, USA.
Olivia MarsicovetereDepartment of Dermatology, Mt Zion Cancer Research Center, University of California San Francisco, San Francisco, CA, USA.
Denise P MuñozDepartment of Hematology-Oncology, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA.
Klemens RappersbergerDepartment of Dermatology, Clinic Landstrasse Vienna, Academic Teaching Hospital, Medical University Vienna, Vienna, Austria.
Jean-Philippe CoppeDepartment of Radiation Oncology, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA.
Susana Ortiz-UrdaDepartment of Dermatology, Mt Zion Cancer Research Center, University of California San Francisco, San Francisco, CA, USA.

Funding

Translational InformaticsP30CA082103 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Alan Ashworth · 1999 to 2026
$209.7M
NCI NIH HHS P30 CA082103
6 · The paper itself

Abstract

backgroundMelanoma is an aggressive form of skin cancer, and patients with NRAS-mutant melanoma face limited treatment options due to the lack of direct NRAS inhibitors. This study explores the utilization of antisense oligonucleotides (ASOs) to directly target NRAS-mRNA for therapeutic approaches.

methodsWe designed and tested NRAS-mRNA-targeting ASOs. Experiments in melanoma cell lines and mouse models assessed effects on cell survival, apoptosis, and tumor growth. A kinase activity profiling platform identified therapeutically exploitable pathways influenced by NRAS suppression.

resultsOur research suggests that ASOs do not need to target the mutated NRAS segment to be effective. ASOs designed for the non-mutated NRAS sequence eliminate NRAS-dependent melanoma cells while sparing NRAS wild-type cells. They act independently of subcellular target localization, reduce NRAS-mRNA levels, inhibit MAPK signaling, induce apoptosis, and suppress melanoma growth in vitro and in vivo. Outcomes of high-throughput kinase activity mapping (HT-KAM) indicate a significant dependency between NRAS-mRNA expression and the activity of MEK1, FGFR2, and CDK4 kinases. Co-targeting these kinases enhances the antiproliferative effect of NRAS ASOs, showing synergy.

conclusionsThese findings highlight antisense oligonucleotides as a promising therapeutic approach for NRAS-mutant melanoma. By effectively blocking NRAS-mRNA, this strategy overcomes challenges posed by the absence of a direct small molecule inhibitor for NRAS, and may offer new treatment options for patients.

Identifiers

PMID40473796
PMCPMC12141655

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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.