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Mutant HRas Signaling and Rationale for Use of Farnesyltransferase Inhibitors in Head and Neck Squamous Cell Carcinoma

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Abstract

Head and neck squamous cell carcinomas (HNSCCs) are often associated with poor outcomes, due at least in part to the limited number of treatment options available for those patients who develop recurrent and/or metastatic disease (R/M HNSCC). Even with the recent validation and approval of immunotherapies in the first-line setting for these patients, the need for the development of new and alternative precision medicine strategies with survival benefit is clear. Oncogenic alterations in the HRAS (Harvey rat sarcoma virus) proto-oncogene are seen in approximately 4–8% of R/M HNSCC tumors. Recently, several preclinical and clinical advancements have been made in the implementation of small-molecule inhibitors that block post-translational farnesylation of HRas, thereby abrogating its downstream oncogenic activity. In this review, we focus on the biology of wild-type and mutant HRas signaling in HNSCC, and rationale for use and outcomes of farnesyltransferase inhibitors in patients with HRAS-mutant tumors.

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Authors and Affiliations

  1. Department of Pharmacology, University of Michigan, Ann Arbor, MI, 48109, USA

    Jiayu Wang & J. Chad Brenner

  2. Department of Otolaryngology-Head and Neck Surgery, University of Michigan, MSRB III 1150 W. Medical Center Dr., Ann Arbor, MI, 48109, USA

    Dana Al-Majid, J. Chad Brenner & Joshua D. Smith

  3. Rogel Cancer Center, University of Michigan, Ann Arbor, MI, 48109, USA

    J. Chad Brenner

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Correspondence to J. Chad Brenner.

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This manuscript benefited from institutional support of the authors by the University of Michigan and the Rogel Cancer Center support grant P30CA046592. JDS received funding support from a National Institutes of Health Training Grant (NIH/NIDCD T32 DC005356) and from an AHNS Presidential Award of the CORE Grants Program of the American Academy of Otolaryngology. JCB was supported by NIH/NIDCR U01-DE029255.

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Jiayu Wang, Dana Al-Majid, J. Chad Brenner, Joshua D. Smith declare they have no conflicts of interest that might be relevant to the contents of this manuscript.

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Wang, J., Al-Majid, D., Brenner, J.C. et al. Mutant HRas Signaling and Rationale for Use of Farnesyltransferase Inhibitors in Head and Neck Squamous Cell Carcinoma. Targ Oncol 18, 643–655 (2023). https://doi.org/10.1007/s11523-023-00993-3

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  • DOI: https://doi.org/10.1007/s11523-023-00993-3

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