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Targeting Melanin in Melanoma with Radionuclide Therapy
Nearly 100,000 individuals are expected to be diagnosed with melanoma in the United States in 2022. Treatment options for late-stage metastatic disease up until the 2010s were few and offered only slight improvement to the overall survival. The introduction of B-RAF inhibitors and anti-CTLA4 and ant...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9455397/ https://www.ncbi.nlm.nih.gov/pubmed/36076924 http://dx.doi.org/10.3390/ijms23179520 |
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author | Allen, Kevin J. H. Malo, Mackenzie E. Jiao, Rubin Dadachova, Ekaterina |
author_facet | Allen, Kevin J. H. Malo, Mackenzie E. Jiao, Rubin Dadachova, Ekaterina |
author_sort | Allen, Kevin J. H. |
collection | PubMed |
description | Nearly 100,000 individuals are expected to be diagnosed with melanoma in the United States in 2022. Treatment options for late-stage metastatic disease up until the 2010s were few and offered only slight improvement to the overall survival. The introduction of B-RAF inhibitors and anti-CTLA4 and anti-PD-1/PD-L1 immunotherapies into standard of care brought measurable increases in the overall survival across all stages of melanoma. Despite the improvement in the survival statistics, patients treated with targeted therapies and immunotherapies are subject to very serious side effects, the development of drug resistance, and the high costs of treatment. This leaves room for the development of novel approaches as well as for the exploration of novel combination therapies for the treatment of metastatic melanoma. One such approach is targeting melanin pigment with radionuclide therapy. Advances in melanin-targeting radionuclide therapy of melanoma can be viewed from two spheres: (1) radioimmunotherapy (RIT) and (2) radiolabeled small molecules. The investigation of mechanisms of the action and efficacy of targeting melanin in melanoma treatment by RIT points to the involvement of the immune system such as complement dependent cytotoxicity. The combination of RIT with immunotherapy presents synergistic killing in mouse melanoma models. The field of radiolabeled small molecules is focused on radioiodinated compounds that have the ability to cross the cellular membranes to access intracellular melanin and can be applied in both therapy and imaging as theranostics. Clinical applications of targeting melanin with radionuclide therapies have produced encouraging results and clinical work is on-going. Continued work on targeting melanin with radionuclide therapy as a monotherapy, or possibly in combination with standard of care agents, has the potential to strengthen the current treatment options for melanoma patients. |
format | Online Article Text |
id | pubmed-9455397 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-94553972022-09-09 Targeting Melanin in Melanoma with Radionuclide Therapy Allen, Kevin J. H. Malo, Mackenzie E. Jiao, Rubin Dadachova, Ekaterina Int J Mol Sci Review Nearly 100,000 individuals are expected to be diagnosed with melanoma in the United States in 2022. Treatment options for late-stage metastatic disease up until the 2010s were few and offered only slight improvement to the overall survival. The introduction of B-RAF inhibitors and anti-CTLA4 and anti-PD-1/PD-L1 immunotherapies into standard of care brought measurable increases in the overall survival across all stages of melanoma. Despite the improvement in the survival statistics, patients treated with targeted therapies and immunotherapies are subject to very serious side effects, the development of drug resistance, and the high costs of treatment. This leaves room for the development of novel approaches as well as for the exploration of novel combination therapies for the treatment of metastatic melanoma. One such approach is targeting melanin pigment with radionuclide therapy. Advances in melanin-targeting radionuclide therapy of melanoma can be viewed from two spheres: (1) radioimmunotherapy (RIT) and (2) radiolabeled small molecules. The investigation of mechanisms of the action and efficacy of targeting melanin in melanoma treatment by RIT points to the involvement of the immune system such as complement dependent cytotoxicity. The combination of RIT with immunotherapy presents synergistic killing in mouse melanoma models. The field of radiolabeled small molecules is focused on radioiodinated compounds that have the ability to cross the cellular membranes to access intracellular melanin and can be applied in both therapy and imaging as theranostics. Clinical applications of targeting melanin with radionuclide therapies have produced encouraging results and clinical work is on-going. Continued work on targeting melanin with radionuclide therapy as a monotherapy, or possibly in combination with standard of care agents, has the potential to strengthen the current treatment options for melanoma patients. MDPI 2022-08-23 /pmc/articles/PMC9455397/ /pubmed/36076924 http://dx.doi.org/10.3390/ijms23179520 Text en © 2022 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 (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Allen, Kevin J. H. Malo, Mackenzie E. Jiao, Rubin Dadachova, Ekaterina Targeting Melanin in Melanoma with Radionuclide Therapy |
title | Targeting Melanin in Melanoma with Radionuclide Therapy |
title_full | Targeting Melanin in Melanoma with Radionuclide Therapy |
title_fullStr | Targeting Melanin in Melanoma with Radionuclide Therapy |
title_full_unstemmed | Targeting Melanin in Melanoma with Radionuclide Therapy |
title_short | Targeting Melanin in Melanoma with Radionuclide Therapy |
title_sort | targeting melanin in melanoma with radionuclide therapy |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9455397/ https://www.ncbi.nlm.nih.gov/pubmed/36076924 http://dx.doi.org/10.3390/ijms23179520 |
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