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DOI: 10.1055/s-0039-1685996
Tipifarnib as a potent therapeutic agent in HRAS-mutated head and neck cancers
HRAS mutations are found in head and neck cancer (HNC) as putative oncogenic drivers. Incidence of HRAS mutations was 4% in TCGA cohorts, and 8% in other screening cohorts. Tipifarnib is a well-known farnesyl transferase inhibitor and was mainly developed as an anti-cancer agent in leukemia therapy. Recently, it proved to be a highly selective inhibitor of HRAS-driven de-differentiated thyroid cancers.
We report on two cases of HNC patients, one squamous cell carcinoma of the oral cavity and one epithelial-myoepithelial carcinoma of the parotid gland. Both patients are in a palliative situation due to progressive metastatic disease after combinatory cytostatic and immunotherapeutic treatments. The patients underwent a HNC biomarker/panel-sequencing program, which was designed by our institution. Furthermore, a Cancer Hotspot Panel addressing mutations of genes like BRAF, HRAS or SMARCB1 was performed. We could detect canonical HRAS mutations and having no other treatment options both patients were referred to a named-patient program including tipifarnib therapy.
Up to now, both patients show partial response to the therapy with rapid and durable significant reduction of tumor volume and tolerable side effects.
Regarding the literature, HRAS mutations are frequently found in HNC, especially in salivary gland cancer. Thus, tipifarnib might be a promising agent for this subgroup of patients, which can be identified by molecular analysis. A phase IIb study on tipifarnib treatment in recurrent and metastatic HRAS-mutated HNC is currently initialized at our Early Clinical Trial Unit.
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Das Medikament Tipifarnib wurde von der Firma Kura Oncology zur Verfügung gestellt.
Publication History
Publication Date:
23 April 2019 (online)
© 2019. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).
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