Immune Checkpoint Inhibitors and RAS–ERK Pathway-Targeted Drugs as Combined Therapy for the Treatment of Melanoma
Metastatic melanoma is a highly immunogenic tumor with very poor survival rates due to immune system escape-mechanisms. Immune checkpoint inhibitors (ICIs) targeting the cytotoxic T-lymphocyte-associated protein 4 (CTLA4) and the programmed death-1 (PD1) receptors, are being used to impede immune ev...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-10-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/12/11/1562 |
| _version_ | 1797468983940612096 |
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| author | Marta Morante Atanasio Pandiella Piero Crespo Ana Herrero |
| author_facet | Marta Morante Atanasio Pandiella Piero Crespo Ana Herrero |
| author_sort | Marta Morante |
| collection | DOAJ |
| description | Metastatic melanoma is a highly immunogenic tumor with very poor survival rates due to immune system escape-mechanisms. Immune checkpoint inhibitors (ICIs) targeting the cytotoxic T-lymphocyte-associated protein 4 (CTLA4) and the programmed death-1 (PD1) receptors, are being used to impede immune evasion. This immunotherapy entails an increment in the overall survival rates. However, melanoma cells respond with evasive molecular mechanisms. ERK cascade inhibitors are also used in metastatic melanoma treatment, with the RAF activity blockade being the main therapeutic approach for such purpose, and in combination with MEK inhibitors improves many parameters of clinical efficacy. Despite their efficacy in inhibiting ERK signaling, the rewiring of the melanoma cell-signaling results in disease relapse, constituting the reinstatement of ERK activation, which is a common cause of some resistance mechanisms. Recent studies revealed that the combination of RAS–ERK pathway inhibitors and ICI therapy present promising advantages for metastatic melanoma treatment. Here, we present a recompilation of the combined therapies clinically evaluated in patients. |
| first_indexed | 2024-03-09T19:14:03Z |
| format | Article |
| id | doaj.art-441d56435c1149489f42e2f6dc78e5d3 |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-09T19:14:03Z |
| publishDate | 2022-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-441d56435c1149489f42e2f6dc78e5d32023-11-24T03:52:39ZengMDPI AGBiomolecules2218-273X2022-10-011211156210.3390/biom12111562Immune Checkpoint Inhibitors and RAS–ERK Pathway-Targeted Drugs as Combined Therapy for the Treatment of MelanomaMarta Morante0Atanasio Pandiella1Piero Crespo2Ana Herrero3Instituto de Biomedicina y Biotecnología de Cantabria (IBBTEC), Consejo Superior de Investigaciones Científicas (CSIC)—Universidad de Cantabria, 39011 Santander, SpainCentro de Investigación Biomédica en Red de Cáncer (CIBERONC), Instituto de Salud Carlos III, 28009 Madrid, SpainInstituto de Biomedicina y Biotecnología de Cantabria (IBBTEC), Consejo Superior de Investigaciones Científicas (CSIC)—Universidad de Cantabria, 39011 Santander, SpainInstituto de Biomedicina y Biotecnología de Cantabria (IBBTEC), Consejo Superior de Investigaciones Científicas (CSIC)—Universidad de Cantabria, 39011 Santander, SpainMetastatic melanoma is a highly immunogenic tumor with very poor survival rates due to immune system escape-mechanisms. Immune checkpoint inhibitors (ICIs) targeting the cytotoxic T-lymphocyte-associated protein 4 (CTLA4) and the programmed death-1 (PD1) receptors, are being used to impede immune evasion. This immunotherapy entails an increment in the overall survival rates. However, melanoma cells respond with evasive molecular mechanisms. ERK cascade inhibitors are also used in metastatic melanoma treatment, with the RAF activity blockade being the main therapeutic approach for such purpose, and in combination with MEK inhibitors improves many parameters of clinical efficacy. Despite their efficacy in inhibiting ERK signaling, the rewiring of the melanoma cell-signaling results in disease relapse, constituting the reinstatement of ERK activation, which is a common cause of some resistance mechanisms. Recent studies revealed that the combination of RAS–ERK pathway inhibitors and ICI therapy present promising advantages for metastatic melanoma treatment. Here, we present a recompilation of the combined therapies clinically evaluated in patients.https://www.mdpi.com/2218-273X/12/11/1562RAS–ERKmelanomainhibitorsimmunotherapy |
| spellingShingle | Marta Morante Atanasio Pandiella Piero Crespo Ana Herrero Immune Checkpoint Inhibitors and RAS–ERK Pathway-Targeted Drugs as Combined Therapy for the Treatment of Melanoma Biomolecules RAS–ERK melanoma inhibitors immunotherapy |
| title | Immune Checkpoint Inhibitors and RAS–ERK Pathway-Targeted Drugs as Combined Therapy for the Treatment of Melanoma |
| title_full | Immune Checkpoint Inhibitors and RAS–ERK Pathway-Targeted Drugs as Combined Therapy for the Treatment of Melanoma |
| title_fullStr | Immune Checkpoint Inhibitors and RAS–ERK Pathway-Targeted Drugs as Combined Therapy for the Treatment of Melanoma |
| title_full_unstemmed | Immune Checkpoint Inhibitors and RAS–ERK Pathway-Targeted Drugs as Combined Therapy for the Treatment of Melanoma |
| title_short | Immune Checkpoint Inhibitors and RAS–ERK Pathway-Targeted Drugs as Combined Therapy for the Treatment of Melanoma |
| title_sort | immune checkpoint inhibitors and ras erk pathway targeted drugs as combined therapy for the treatment of melanoma |
| topic | RAS–ERK melanoma inhibitors immunotherapy |
| url | https://www.mdpi.com/2218-273X/12/11/1562 |
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