PXD062989-1

PXD062989 is an original dataset announced via ProteomeXchange.

Title	Kinome profiling of HRAS Q61K mutant SMS-CTR rhabdomyosarcoma cell line treated with tipifarnib
Description	Hyperactive RAS signaling drives tumorigenesis in PAX 3/7::FOXO1 fusion-negative rhabdomyosarcoma (FN-RMS). Despite the frequency of these mutations, RAS pathway-directed therapies have been ineffective for RAS-driven RMS. Farnesyltransferase (FTase) inhibitors (FTIs), such as tipifarnib, inhibit HRAS membrane localization and blunt HRAS effector signaling, leading to an antitumor effect in HRAS-mutant FN-RMS preclinical models. Response to FTI is limited by adaptive feedback reactivation of ERK signaling and upregulation of wild-type (WT) RAS. We found that the combination of HRAS suppression with FTI and MEK inhibition (MEKi) impaired ERK reactivation and reduced ERK transcriptional output in HRAS-mutant RMS models. Co-targeting FTase and MEK restrained tumor progression and induced terminal myogenic differentiation. These findings highlight an effective combinatorial strategy and support its preclinical translation for patients with HRAS-mutant RMS. Here, kinome profiling was performed on the SMS-CTR(HRAS Q61K) RMS cell line after 24 or 48 hour exposure to 100 nM tipifarnib.
HostingRepository	PRIDE
AnnounceDate	2026-02-12
AnnouncementXML	Submission_2026-02-12_08:37:13.450.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Steven Angus
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2025-04-15 08:51:15	ID requested
⏵ 1	2026-02-12 08:37:14	announced

Odeniyide P, Skaist A, Fenner E, Amirkhanian H, Baker A, Lisok A, Zhang L, Fridman L, Rojas RI, Hebron KE, Davis C, Zhang X, Feldman G, Angus SP, Thomas CJ, Vaseva AV, Yohe ME, Fertig EJ, Pratilas CA, Combined Inhibition of HRAS and MEK Induces Tumor Regression and Restores Myogenic Differentiation in HRAS-Mutant Rhabdomyosarcoma. Cancer Res, ():(2026) [pubmed]

10.1158/0008-5472.can-25-2985;

submitter keyword: MAPK pathway, MEK inhibition,RAS, farnesyltransferase inhibitor, tumor

Christine Pratilas
contact affiliation	Department of Oncology, Sidney Kimmel Comprehensive Cancer Center and Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA
contact email	cpratil1@jhmi.edu
lab head
Steven Angus
contact affiliation	Indiana University School of Medicine
contact email	sangus@iu.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD062989
     1. Label: PRIDE project
     2. Name: Kinome profiling of HRAS Q61K mutant SMS-CTR rhabdomyosarcoma cell line treated with tipifarnib