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...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-08-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/17/9520 |
| _version_ | 1797495354777665536 |
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| author | Kevin J. H. Allen Mackenzie E. Malo Rubin Jiao Ekaterina Dadachova |
| author_facet | Kevin J. H. Allen Mackenzie E. Malo Rubin Jiao Ekaterina Dadachova |
| author_sort | Kevin J. H. Allen |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-10T01:47:38Z |
| format | Article |
| id | doaj.art-f069825c2efd4a39bb40d824d89aaa71 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T01:47:38Z |
| publishDate | 2022-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-f069825c2efd4a39bb40d824d89aaa712023-11-23T13:12:12ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-08-012317952010.3390/ijms23179520Targeting Melanin in Melanoma with Radionuclide TherapyKevin J. H. Allen0Mackenzie E. Malo1Rubin Jiao2Ekaterina Dadachova3College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, SK S7N 5E5, CanadaCollege of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, SK S7N 5E5, CanadaCollege of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, SK S7N 5E5, CanadaCollege of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, SK S7N 5E5, CanadaNearly 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.https://www.mdpi.com/1422-0067/23/17/9520metastatic melanomaradioimmunotherapymelanintargeted radionuclide therapybenzamidesnicotinamides |
| spellingShingle | Kevin J. H. Allen Mackenzie E. Malo Rubin Jiao Ekaterina Dadachova Targeting Melanin in Melanoma with Radionuclide Therapy International Journal of Molecular Sciences metastatic melanoma radioimmunotherapy melanin targeted radionuclide therapy benzamides nicotinamides |
| 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 | metastatic melanoma radioimmunotherapy melanin targeted radionuclide therapy benzamides nicotinamides |
| url | https://www.mdpi.com/1422-0067/23/17/9520 |
| work_keys_str_mv | AT kevinjhallen targetingmelanininmelanomawithradionuclidetherapy AT mackenzieemalo targetingmelanininmelanomawithradionuclidetherapy AT rubinjiao targetingmelanininmelanomawithradionuclidetherapy AT ekaterinadadachova targetingmelanininmelanomawithradionuclidetherapy |