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Treatment of Cutaneous Melanoma Harboring SMO p.Gln216Arg Mutation with Imiquimod: An Old Drug with New Results

Melanoma is the most lethal form of skin cancer and its incidence is growing worldwide. In the last ten years, the therapeutic scenario of this disease has been revolutionized by the introduction of targeted therapies and immune-checkpoint inhibitors. However, in patients with many lesions and bulky...

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Autores principales: Troiani, Teresa, Napolitano, Stefania, Brancaccio, Gabriella, Belli, Valentina, Nappi, Annarita, Miro, Caterina, Salvatore, Domenico, Dentice, Monica, Caraglia, Michele, Franco, Renato, Giunta, Emilio Francesco, De Falco, Vincenzo, Ciardiello, Davide, Ciardiello, Fortunato, Argenziano, Giuseppe
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8000647/
https://www.ncbi.nlm.nih.gov/pubmed/33799349
http://dx.doi.org/10.3390/jpm11030206
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author Troiani, Teresa
Napolitano, Stefania
Brancaccio, Gabriella
Belli, Valentina
Nappi, Annarita
Miro, Caterina
Salvatore, Domenico
Dentice, Monica
Caraglia, Michele
Franco, Renato
Giunta, Emilio Francesco
De Falco, Vincenzo
Ciardiello, Davide
Ciardiello, Fortunato
Argenziano, Giuseppe
author_facet Troiani, Teresa
Napolitano, Stefania
Brancaccio, Gabriella
Belli, Valentina
Nappi, Annarita
Miro, Caterina
Salvatore, Domenico
Dentice, Monica
Caraglia, Michele
Franco, Renato
Giunta, Emilio Francesco
De Falco, Vincenzo
Ciardiello, Davide
Ciardiello, Fortunato
Argenziano, Giuseppe
author_sort Troiani, Teresa
collection PubMed
description Melanoma is the most lethal form of skin cancer and its incidence is growing worldwide. In the last ten years, the therapeutic scenario of this disease has been revolutionized by the introduction of targeted therapies and immune-checkpoint inhibitors. However, in patients with many lesions and bulky tumors, in which surgery is no longer feasible, there is a need for new treatment options. Here we report, for the first time to our knowledge, a clinical case where a melanoma patient harboring the SMO p.Gln216Arg mutation has been treated with imiquimod, showing a complete and durable response. To better explain this outstanding response to the treatment, we transfected a melanoma cell line (MeWo) with the SMO p.Gln216Arg mutation in order to evaluate its role in response to the imiquimod treatment. Moreover, to better demonstrate that the antitumor activity of imiquimod was due to its role in suppressing the oncogenic SMO signaling pathway, independently of its immune modulating function, an in vivo experiment has been performed. This clinical case opens up a new scenario for the treatment of melanoma patients identifying a new potentially druggable target.
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spelling pubmed-80006472021-03-28 Treatment of Cutaneous Melanoma Harboring SMO p.Gln216Arg Mutation with Imiquimod: An Old Drug with New Results Troiani, Teresa Napolitano, Stefania Brancaccio, Gabriella Belli, Valentina Nappi, Annarita Miro, Caterina Salvatore, Domenico Dentice, Monica Caraglia, Michele Franco, Renato Giunta, Emilio Francesco De Falco, Vincenzo Ciardiello, Davide Ciardiello, Fortunato Argenziano, Giuseppe J Pers Med Case Report Melanoma is the most lethal form of skin cancer and its incidence is growing worldwide. In the last ten years, the therapeutic scenario of this disease has been revolutionized by the introduction of targeted therapies and immune-checkpoint inhibitors. However, in patients with many lesions and bulky tumors, in which surgery is no longer feasible, there is a need for new treatment options. Here we report, for the first time to our knowledge, a clinical case where a melanoma patient harboring the SMO p.Gln216Arg mutation has been treated with imiquimod, showing a complete and durable response. To better explain this outstanding response to the treatment, we transfected a melanoma cell line (MeWo) with the SMO p.Gln216Arg mutation in order to evaluate its role in response to the imiquimod treatment. Moreover, to better demonstrate that the antitumor activity of imiquimod was due to its role in suppressing the oncogenic SMO signaling pathway, independently of its immune modulating function, an in vivo experiment has been performed. This clinical case opens up a new scenario for the treatment of melanoma patients identifying a new potentially druggable target. MDPI 2021-03-14 /pmc/articles/PMC8000647/ /pubmed/33799349 http://dx.doi.org/10.3390/jpm11030206 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ).
spellingShingle Case Report
Troiani, Teresa
Napolitano, Stefania
Brancaccio, Gabriella
Belli, Valentina
Nappi, Annarita
Miro, Caterina
Salvatore, Domenico
Dentice, Monica
Caraglia, Michele
Franco, Renato
Giunta, Emilio Francesco
De Falco, Vincenzo
Ciardiello, Davide
Ciardiello, Fortunato
Argenziano, Giuseppe
Treatment of Cutaneous Melanoma Harboring SMO p.Gln216Arg Mutation with Imiquimod: An Old Drug with New Results
title Treatment of Cutaneous Melanoma Harboring SMO p.Gln216Arg Mutation with Imiquimod: An Old Drug with New Results
title_full Treatment of Cutaneous Melanoma Harboring SMO p.Gln216Arg Mutation with Imiquimod: An Old Drug with New Results
title_fullStr Treatment of Cutaneous Melanoma Harboring SMO p.Gln216Arg Mutation with Imiquimod: An Old Drug with New Results
title_full_unstemmed Treatment of Cutaneous Melanoma Harboring SMO p.Gln216Arg Mutation with Imiquimod: An Old Drug with New Results
title_short Treatment of Cutaneous Melanoma Harboring SMO p.Gln216Arg Mutation with Imiquimod: An Old Drug with New Results
title_sort treatment of cutaneous melanoma harboring smo p.gln216arg mutation with imiquimod: an old drug with new results
topic Case Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8000647/
https://www.ncbi.nlm.nih.gov/pubmed/33799349
http://dx.doi.org/10.3390/jpm11030206
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