Potential of Farnesyl Transferase Inhibitors in Combination Regimens in Squamous Cell Carcinomas

Current therapies for recurrent and metastatic SCC are associated with poor outcomes, and options for later lines of treatment are limited. Insights into potential therapeutic targets, as well as mechanisms of resistance to available therapies, have begun to be elucidated, creating the basis for exp...

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Autores principales:	Linda Kessler, Shivani Malik, Mollie Leoni, Francis Burrows
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	HNSCC farnesyl transferase tipifarnib combination regimen Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/788d638e52cd42a7b9d103cf883e0e5b
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spelling	oai:doaj.org-article:788d638e52cd42a7b9d103cf883e0e5b2021-11-11T15:28:04ZPotential of Farnesyl Transferase Inhibitors in Combination Regimens in Squamous Cell Carcinomas10.3390/cancers132153102072-6694https://doaj.org/article/788d638e52cd42a7b9d103cf883e0e5b2021-10-01T00:00:00Zhttps://www.mdpi.com/2072-6694/13/21/5310https://doaj.org/toc/2072-6694Current therapies for recurrent and metastatic SCC are associated with poor outcomes, and options for later lines of treatment are limited. Insights into potential therapeutic targets, as well as mechanisms of resistance to available therapies, have begun to be elucidated, creating the basis for exploration of combination approaches to drive better patient outcomes. Tipifarnib, a farnesyl transferase inhibitor (FTI), is a small molecule drug that has demonstrated encouraging clinical activity in a genetically-defined subset of head and neck squamous cell carcinoma (HNSCC)–specifically, tumors that express a mutation in the <i>HRAS</i> protooncogene. More recently, bioinformatic analyses and results from patient-derived xenograft modeling indicate that HRAS pathway dependency may extend to a broader subpopulation of SCCs beyond HRAS mutants in the context of combination with agents such as cisplatin, cetuximab, or alpelisib. In addition, tipifarnib can also inactivate additional farnesylated proteins implicated in resistance to approved therapies, including immunotherapies, through a variety of distinct mechanisms, suggesting that tipifarnib could serve as an anchor for combination regimens in SCCs and other tumor types.Linda KesslerShivani MalikMollie LeoniFrancis BurrowsMDPI AGarticleHNSCCfarnesyl transferasetipifarnibcombination regimenNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENCancers, Vol 13, Iss 5310, p 5310 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	HNSCC farnesyl transferase tipifarnib combination regimen Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	HNSCC farnesyl transferase tipifarnib combination regimen Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Linda Kessler Shivani Malik Mollie Leoni Francis Burrows Potential of Farnesyl Transferase Inhibitors in Combination Regimens in Squamous Cell Carcinomas
description	Current therapies for recurrent and metastatic SCC are associated with poor outcomes, and options for later lines of treatment are limited. Insights into potential therapeutic targets, as well as mechanisms of resistance to available therapies, have begun to be elucidated, creating the basis for exploration of combination approaches to drive better patient outcomes. Tipifarnib, a farnesyl transferase inhibitor (FTI), is a small molecule drug that has demonstrated encouraging clinical activity in a genetically-defined subset of head and neck squamous cell carcinoma (HNSCC)–specifically, tumors that express a mutation in the <i>HRAS</i> protooncogene. More recently, bioinformatic analyses and results from patient-derived xenograft modeling indicate that HRAS pathway dependency may extend to a broader subpopulation of SCCs beyond HRAS mutants in the context of combination with agents such as cisplatin, cetuximab, or alpelisib. In addition, tipifarnib can also inactivate additional farnesylated proteins implicated in resistance to approved therapies, including immunotherapies, through a variety of distinct mechanisms, suggesting that tipifarnib could serve as an anchor for combination regimens in SCCs and other tumor types.
format	article
author	Linda Kessler Shivani Malik Mollie Leoni Francis Burrows
author_facet	Linda Kessler Shivani Malik Mollie Leoni Francis Burrows
author_sort	Linda Kessler
title	Potential of Farnesyl Transferase Inhibitors in Combination Regimens in Squamous Cell Carcinomas
title_short	Potential of Farnesyl Transferase Inhibitors in Combination Regimens in Squamous Cell Carcinomas
title_full	Potential of Farnesyl Transferase Inhibitors in Combination Regimens in Squamous Cell Carcinomas
title_fullStr	Potential of Farnesyl Transferase Inhibitors in Combination Regimens in Squamous Cell Carcinomas
title_full_unstemmed	Potential of Farnesyl Transferase Inhibitors in Combination Regimens in Squamous Cell Carcinomas
title_sort	potential of farnesyl transferase inhibitors in combination regimens in squamous cell carcinomas
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/788d638e52cd42a7b9d103cf883e0e5b
work_keys_str_mv	AT lindakessler potentialoffarnesyltransferaseinhibitorsincombinationregimensinsquamouscellcarcinomas AT shivanimalik potentialoffarnesyltransferaseinhibitorsincombinationregimensinsquamouscellcarcinomas AT mollieleoni potentialoffarnesyltransferaseinhibitorsincombinationregimensinsquamouscellcarcinomas AT francisburrows potentialoffarnesyltransferaseinhibitorsincombinationregimensinsquamouscellcarcinomas
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Potential of Farnesyl Transferase Inhibitors in Combination Regimens in Squamous Cell Carcinomas

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