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Therapeutic Advancements Across Clinical Stages in Melanoma, With a Focus on Targeted Immunotherapy

Melanoma is the most fatal skin cancer. In the early stages, it can be safely treated with surgery alone. However, since 2011, there has been an important revolution in the treatment of melanoma with new effective treatments. Targeted therapy and immunotherapy with checkpoint inhibitors have changed...

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Autores principales: Trojaniello, Claudia, Luke, Jason J., Ascierto, Paolo A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8222774/
https://www.ncbi.nlm.nih.gov/pubmed/34178657
http://dx.doi.org/10.3389/fonc.2021.670726
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author Trojaniello, Claudia
Luke, Jason J.
Ascierto, Paolo A.
author_facet Trojaniello, Claudia
Luke, Jason J.
Ascierto, Paolo A.
author_sort Trojaniello, Claudia
collection PubMed
description Melanoma is the most fatal skin cancer. In the early stages, it can be safely treated with surgery alone. However, since 2011, there has been an important revolution in the treatment of melanoma with new effective treatments. Targeted therapy and immunotherapy with checkpoint inhibitors have changed the history of this disease. To date, more than half of advanced melanoma patients are alive at 5 years; despite this breakthrough, approximately half of the patients still do not respond to treatment. For these reasons, new therapeutic strategies are required to expand the number of patients who can benefit from immunotherapy or combination with targeted therapy. Current research aims at preventing primary and acquired resistance, which are both responsible for treatment failure in about 50% of patients. This could increase the effectiveness of available drugs and allow for the evaluation of new combinations and new targets. The main pathways and molecules under study are the IDO inhibitor, TLR9 agonist, STING, LAG-3, TIM-3, HDAC inhibitors, pegylated IL-2 (NKTR-214), GITR, and adenosine pathway inhibitors, among others (there are currently about 3000 trials that are evaluating immunotherapeutic combinations in different tumors). Other promising strategies are cancer vaccines and oncolytic viruses. Another approach is to isolate and remove immune cells (DCs, T cells, and NK cells) from the patient’s blood or tumor infiltrates, add specific gene fragments, expand them in culture with growth factors, and re-inoculate into the same patient. TILs, TCR gene transfer, and CAR-T therapy follow this approach. In this article, we give an overview over the current status of melanoma therapies, the clinical rationale for choosing treatments, and the new immunotherapy approaches.
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spelling pubmed-82227742021-06-25 Therapeutic Advancements Across Clinical Stages in Melanoma, With a Focus on Targeted Immunotherapy Trojaniello, Claudia Luke, Jason J. Ascierto, Paolo A. Front Oncol Oncology Melanoma is the most fatal skin cancer. In the early stages, it can be safely treated with surgery alone. However, since 2011, there has been an important revolution in the treatment of melanoma with new effective treatments. Targeted therapy and immunotherapy with checkpoint inhibitors have changed the history of this disease. To date, more than half of advanced melanoma patients are alive at 5 years; despite this breakthrough, approximately half of the patients still do not respond to treatment. For these reasons, new therapeutic strategies are required to expand the number of patients who can benefit from immunotherapy or combination with targeted therapy. Current research aims at preventing primary and acquired resistance, which are both responsible for treatment failure in about 50% of patients. This could increase the effectiveness of available drugs and allow for the evaluation of new combinations and new targets. The main pathways and molecules under study are the IDO inhibitor, TLR9 agonist, STING, LAG-3, TIM-3, HDAC inhibitors, pegylated IL-2 (NKTR-214), GITR, and adenosine pathway inhibitors, among others (there are currently about 3000 trials that are evaluating immunotherapeutic combinations in different tumors). Other promising strategies are cancer vaccines and oncolytic viruses. Another approach is to isolate and remove immune cells (DCs, T cells, and NK cells) from the patient’s blood or tumor infiltrates, add specific gene fragments, expand them in culture with growth factors, and re-inoculate into the same patient. TILs, TCR gene transfer, and CAR-T therapy follow this approach. In this article, we give an overview over the current status of melanoma therapies, the clinical rationale for choosing treatments, and the new immunotherapy approaches. Frontiers Media S.A. 2021-06-10 /pmc/articles/PMC8222774/ /pubmed/34178657 http://dx.doi.org/10.3389/fonc.2021.670726 Text en Copyright © 2021 Trojaniello, Luke and Ascierto https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Trojaniello, Claudia
Luke, Jason J.
Ascierto, Paolo A.
Therapeutic Advancements Across Clinical Stages in Melanoma, With a Focus on Targeted Immunotherapy
title Therapeutic Advancements Across Clinical Stages in Melanoma, With a Focus on Targeted Immunotherapy
title_full Therapeutic Advancements Across Clinical Stages in Melanoma, With a Focus on Targeted Immunotherapy
title_fullStr Therapeutic Advancements Across Clinical Stages in Melanoma, With a Focus on Targeted Immunotherapy
title_full_unstemmed Therapeutic Advancements Across Clinical Stages in Melanoma, With a Focus on Targeted Immunotherapy
title_short Therapeutic Advancements Across Clinical Stages in Melanoma, With a Focus on Targeted Immunotherapy
title_sort therapeutic advancements across clinical stages in melanoma, with a focus on targeted immunotherapy
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8222774/
https://www.ncbi.nlm.nih.gov/pubmed/34178657
http://dx.doi.org/10.3389/fonc.2021.670726
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