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Case Report
Durable response to tipifarnib in a patient with refractory head and neck cancer with a HRAS mutation: A case report
1 Willamette Valley Cancer Institute and Research Center, Eugene, OR 97401, USA
2 Department of Oncology, Mayo Clinic, Rochester, MN 55905, USA
3 Division of Hematology, Mayo Clinic, Rochester, MN 55905, USA
Address correspondence to:
Jennifer J Gile
MD, Willamette Valley Cancer Institute and Research Center, 520 Country Club Rd, Eugene, OR 97401,
USA
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Article ID: 100159Z10JG2026
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Gile JJ, Price K, Baral B, Witzig TE. Durable response to tipifarnib in a patient with refractory head and neck cancer with a HRAS mutation: A case report. J Case Rep Images Oncology 2026;12(2):8–12.ABSTRACT
Introduction: Head and neck squamous cell carcinoma (HNSCC) remains a clinically challenging malignancy, particularly in the recurrent or metastatic setting after progression on multimodality therapy. Activating health reimbursement arrangement (HRAS) mutations occur in approximately 4–8% of HNSCC and represent a potentially actionable target. Tipifarnib, an oral farnesyltransferase inhibitor, has demonstrated promising activity in HRAS-mutant tumors but is not commercially available despite prior Breakthrough Therapy designation.
Case Report: We report the case of a 48-year-old woman with recurrent, treatment-refractory oral cavity squamous cell carcinoma who experienced a dramatic and durable response to tipifarnib. Following initial treatment, she developed rapid locoregional recurrence requiring tracheostomy. Her disease progressed through multiple lines of therapy. Comprehensive next-generation sequencing of recurrent tumor tissue revealed an HRAS mutation. Given lack of response to prior checkpoint inhibitors, compassionate use of tipifarnib was initiated. The patient experienced a near-complete response within two months and achieved a complete response by 12 months and continues to remain disease free almost two years after therapy initiation with excellent functional recovery and manageable toxicity limited primarily to neutropenia.
Conclusion: This case highlights the transformative potential of precision oncology in refractory HNSCC. Broader access to HRAS-targeted therapies and prospective validation of molecular predictors are urgently needed to improve outcomes in this molecularly defined subset.
Keywords: Farnesyltransferase inhibitor, Head and neck squamous cell carcinoma, HRAS mutation, Precision oncology, Tipifarnib
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Acknowledgments
No artificial intelligence writing tools were used in preparation of the manuscript.
Author ContributionsJennifer J Gile - Substantial contributions to conception and design, Interpretation of data, Drafting the article, Revising it critically for important intellectual content, Final approval of the version to be published
Katharine Price - Substantial contributions to conception and design, Interpretation of data, Drafting the article, Revising it critically for important intellectual content, Final approval of the version to be published
Binav Baral - Substantial contributions to conception and design, Drafting the article, Revising it critically for important intellectual content, Final approval of the version to be published
Thomas E Witzig - Substantial contributions to conception and design, Analysis of data, Interpretation of data, Drafting the article, Revising it critically for important intellectual content, Final approval of the version to be published
Guaranter of SubmissionThe corresponding author is the guarantor of submission.
Source of SupportNone
Consent StatementWritten informed consent was obtained from the patient for publication of this article.
Data AvailabilityAll relevant data are within the paper and its Supporting Information files.
Conflict of InterestAuthors declare no conflict of interest.
Copyright© 2026 Jennifer J Gile et al. This article is distributed under the terms of Creative Commons Attribution License which permits unrestricted use, distribution and reproduction in any medium provided the original author(s) and original publisher are properly credited. Please see the copyright policy on the journal website for more information.
