ArticleOncogene2022
Targeting farnesylation as a novel therapeutic approach in HRAS-mutant rhabdomyosarcoma.
Article in Oncogene, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 28 papers.
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.
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.
Who cites it
28 citing papers in PubMed, 41 citations in OpenAlex.
- Combined Inhibition of HRAS and MEK Induces Tumor Regression and Restores Myogenic Differentiation in HRAS-Mutant Rhabdomyosarcoma.Cancer research · 2026Article
- Activity of Direct KRAS(G12C) Inhibitors in Preclinical Models of Pediatric Cancer.Molecular cancer therapeutics · 2026Article
- Review
- PCSK5M452I Is a Recessive Hypomorph Exclusive to MCF10DCIS.com Cells.Molecular cancer research : MCR · 2026Article
- Integrative computational approach to farnesyltransferase inhibition toward anti-liver cancer drug candidate fromMolecular biology research communications · 2026Article
- The E2F1-HMGCR axis promotes ferroptosis resistance in immune refractory tumor cells.Nature communications · 2025Article
- Farnesyltransferase inhibitors decrease matrix-vesicle-mediated mineralization in SaOS-2 cells.Molecular biology reports · 2025Article
- Wild-type RAS signaling is an essential therapeutic target inScience signaling · 2025Article
- RAS-membrane interaction and oligomerization: there is more than meets the eye.Biochemical Society transactions · 2025Review
- Review
- The complex journey of targeting RAS in oncology.BMC cancer · 2025Review
- Protein lipidation in the tumor microenvironment: enzymology, signaling pathways, and therapeutics.Molecular cancer · 2025Review
- Impaired MC3T3-E1 osteoblast differentiation triggered by oncogenic HRAS is rescued by the farnesyltransferase inhibitor Tipifarnib.Scientific reports · 2025Article
- Use of 3' Rapid Amplification of cDNA Ends (3' RACE)-Based Targeted RNA Sequencing for Profiling of Druggable Genetic Alterations in Urothelial Carcinomas.International journal of molecular sciences · 2024Article
- NINJ1 regulates ferroptosis via xCT antiporter interaction and CoA modulation.Cell death & disease · 2024Article
- Genomic profiles of Japanese patients with vulvar squamous cell carcinoma.Scientific reports · 2024Article
- Targeted genetic and small molecule disruption of N-Ras CaaX cleavage alters its localization and oncogenic potential.Bioorganic chemistry · 2024Article
- Statins as anti-tumor agents: A paradigm for repurposed drugs.Cancer reports (Hoboken, N.J.) · 2024Review
- Article
- Thioredoxin (Trx): A redox target and modulator of cellular senescence and aging-related diseases.Redox biology · 2024Review
Corrections and comments
- Erratum issued
Authors and funding
15 authors at 5 institutions in 1 country.
Funding
Abstract
Activating RAS mutations are found in a subset of fusion-negative rhabdomyosarcoma (RMS), and therapeutic strategies to directly target RAS in these tumors have been investigated, without clinical success to date. A potential strategy to inhibit oncogenic RAS activity is the disruption of RAS prenylation, an obligate step for RAS membrane localization and effector pathway signaling, through inhibition of farnesyltransferase (FTase). Of the major RAS family members, HRAS is uniquely dependent on FTase for prenylation, whereas NRAS and KRAS can utilize geranylgeranyl transferase as a bypass prenylation mechanism. Tumors driven by oncogenic HRAS may therefore be uniquely sensitive to FTase inhibition. To investigate the mutation-specific effects of FTase inhibition in RMS we utilized tipifarnib, a potent and selective FTase inhibitor, in in vitro and in vivo models of RMS genomically characterized for RAS mutation status. Tipifarnib reduced HRAS processing, and plasma membrane localization leading to decreased GTP-bound HRAS and decreased signaling through RAS effector pathways. In HRAS-mutant cell lines, tipifarnib reduced two-dimensional and three-dimensional cell growth, and in vivo treatment with tipifarnib resulted in tumor growth inhibition exclusively in HRAS-mutant RMS xenografts. Our data suggest that small molecule inhibition of FTase is active in HRAS-driven RMS and may represent an effective therapeutic strategy for a genomically-defined subset of patients with RMS.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.