biostudies-literatureJagadeeshan SUniversity of ChicagoCouncil for Higher EducationIsrael Science FoundationNational Natural Science Foundation of ChinaNational Cancer InstituteNCI NIH HHSNational Institutes of HealthIsrael Cancer Research Fund106688https://www.ebi.ac.uk/biostudies/studies/S-EPMC11309563biostudies-literatureUnknown149Head and neck squamous cell carcinoma (HNSCC) is a highly prevalent malignancy worldwide, with a significant proportion of patients developing recurrent and/or metastatic (R/M) disease. Despite recent advances in therapy, the prognosis for patients with advanced HNSCC remains poor. Here, we present the case of a patient with recurrent metastatic HNSCC harboring an HRAS G12S mutation who achieved a durable response to treatment with tipifarnib, a selective inhibitor of farnesyltransferase. The patient was a 48-year-old woman who had previously received multiple lines of therapy with no significant clinical response. However, treatment with tipifarnib resulted in a durable partial response that lasted 8 months. Serial genomic and transcriptomic analyses demonstrated upregulation of YAP1 and Oral oncologyEvolutionary dynamics of tipifarnib in HRAS mutated head and neck squamous cell carcinoma.PMC11309563P30 CA00874817-1693-RCDA3409/20P30 CA014599Shaposhnikov KBednyagin LShin NShugaev-Mendosa EKessler LPeterson ATsareva AElkabets MYunusova LHo ALBurrows FMathukkada SMelikhova DIzumchenko ECole GPearson ATBoyko ASuryamohan KRosenberg AJPravdivtseva EStupichev DJagadeeshan SAgrawal NfalseEvolutionary dynamics of tipifarnib in HRAS mutated head and neck squamous cell carcinoma.Head and neck squamous cell carcinoma (HNSCC) is a highly prevalent malignancy worldwide, with a significant proportion of patients developing recurrent and/or metastatic (R/M) disease. Despite recent advances in therapy, the prognosis for patients with advanced HNSCC remains poor. Here, we present the case of a patient with recurrent metastatic HNSCC harboring an HRAS G12S mutation who achieved a durable response to treatment with tipifarnib, a selective inhibitor of farnesyltransferase. The patient was a 48-year-old woman who had previously received multiple lines of therapy with no significant clinical response. However, treatment with tipifarnib resulted in a durable partial response that lasted 8 months. Serial genomic and transcriptomic analyses demonstrated upregulation of YAP1 and 2024-01-01T00:00:00Z2024 Feb2026-06-02T11:58:59.796Z2025-04-03T23:22:49.049ZS-EPMC113095633821970610.1016/j.oraloncology.2024.106688