Enhancing Therapeutic Approaches for Melanoma Patients Targeting Epigenetic Modifiers
Melanoma is the least common but deadliest type of skin cancer. Melanomagenesis is driven by a series of mutations and epigenetic alterations in oncogenes and tumor suppressor genes that allow melanomas to grow, evolve, and metastasize. Epigenetic alterations can also lead to immune evasion and deve...
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-12-01
|
| Series: | Cancers |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2072-6694/13/24/6180 |
| _version_ | 1797506394397605888 |
|---|---|
| author | Maria Gracia-Hernandez Zuleima Munoz Alejandro Villagra |
| author_facet | Maria Gracia-Hernandez Zuleima Munoz Alejandro Villagra |
| author_sort | Maria Gracia-Hernandez |
| collection | DOAJ |
| description | Melanoma is the least common but deadliest type of skin cancer. Melanomagenesis is driven by a series of mutations and epigenetic alterations in oncogenes and tumor suppressor genes that allow melanomas to grow, evolve, and metastasize. Epigenetic alterations can also lead to immune evasion and development of resistance to therapies. Although the standard of care for melanoma patients includes surgery, targeted therapies, and immune checkpoint blockade, other therapeutic approaches like radiation therapy, chemotherapy, and immune cell-based therapies are used for patients with advanced disease or unresponsive to the conventional first-line therapies. Targeted therapies such as the use of BRAF and MEK inhibitors and immune checkpoint inhibitors such as anti-PD-1 and anti-CTLA4 only improve the survival of a small subset of patients. Thus, there is an urgent need to identify alternative standalone or combinatorial therapies. Epigenetic modifiers have gained attention as therapeutic targets as they modulate multiple cellular and immune-related processes. Due to melanoma’s susceptibility to extrinsic factors and reversible nature, epigenetic drugs are investigated as a therapeutic avenue and as adjuvants for targeted therapies and immune checkpoint inhibitors, as they can sensitize and/or reverse resistance to these therapies, thus enhancing their therapeutic efficacy. This review gives an overview of the role of epigenetic changes in melanoma progression and resistance. In addition, we evaluate the latest advances in preclinical and clinical research studying combinatorial therapies and discuss the use of epigenetic drugs such as HDAC and DNMT inhibitors as potential adjuvants for melanoma patients. |
| first_indexed | 2024-03-10T04:32:03Z |
| format | Article |
| id | doaj.art-ad17ffc1d5af46a19f1bc1a220cf67d8 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T04:32:03Z |
| publishDate | 2021-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-ad17ffc1d5af46a19f1bc1a220cf67d82023-11-23T04:04:50ZengMDPI AGCancers2072-66942021-12-011324618010.3390/cancers13246180Enhancing Therapeutic Approaches for Melanoma Patients Targeting Epigenetic ModifiersMaria Gracia-Hernandez0Zuleima Munoz1Alejandro Villagra2Department of Biochemistry and Molecular Medicine, School of Medicine and Health Sciences, The George Washington University, Washington, DC 20052, USADepartment of Biochemistry and Molecular Medicine, School of Medicine and Health Sciences, The George Washington University, Washington, DC 20052, USADepartment of Biochemistry and Molecular Medicine, School of Medicine and Health Sciences, The George Washington University, Washington, DC 20052, USAMelanoma is the least common but deadliest type of skin cancer. Melanomagenesis is driven by a series of mutations and epigenetic alterations in oncogenes and tumor suppressor genes that allow melanomas to grow, evolve, and metastasize. Epigenetic alterations can also lead to immune evasion and development of resistance to therapies. Although the standard of care for melanoma patients includes surgery, targeted therapies, and immune checkpoint blockade, other therapeutic approaches like radiation therapy, chemotherapy, and immune cell-based therapies are used for patients with advanced disease or unresponsive to the conventional first-line therapies. Targeted therapies such as the use of BRAF and MEK inhibitors and immune checkpoint inhibitors such as anti-PD-1 and anti-CTLA4 only improve the survival of a small subset of patients. Thus, there is an urgent need to identify alternative standalone or combinatorial therapies. Epigenetic modifiers have gained attention as therapeutic targets as they modulate multiple cellular and immune-related processes. Due to melanoma’s susceptibility to extrinsic factors and reversible nature, epigenetic drugs are investigated as a therapeutic avenue and as adjuvants for targeted therapies and immune checkpoint inhibitors, as they can sensitize and/or reverse resistance to these therapies, thus enhancing their therapeutic efficacy. This review gives an overview of the role of epigenetic changes in melanoma progression and resistance. In addition, we evaluate the latest advances in preclinical and clinical research studying combinatorial therapies and discuss the use of epigenetic drugs such as HDAC and DNMT inhibitors as potential adjuvants for melanoma patients.https://www.mdpi.com/2072-6694/13/24/6180epigeneticsmelanomaacetylationmethylationcombination therapyresistance |
| spellingShingle | Maria Gracia-Hernandez Zuleima Munoz Alejandro Villagra Enhancing Therapeutic Approaches for Melanoma Patients Targeting Epigenetic Modifiers Cancers epigenetics melanoma acetylation methylation combination therapy resistance |
| title | Enhancing Therapeutic Approaches for Melanoma Patients Targeting Epigenetic Modifiers |
| title_full | Enhancing Therapeutic Approaches for Melanoma Patients Targeting Epigenetic Modifiers |
| title_fullStr | Enhancing Therapeutic Approaches for Melanoma Patients Targeting Epigenetic Modifiers |
| title_full_unstemmed | Enhancing Therapeutic Approaches for Melanoma Patients Targeting Epigenetic Modifiers |
| title_short | Enhancing Therapeutic Approaches for Melanoma Patients Targeting Epigenetic Modifiers |
| title_sort | enhancing therapeutic approaches for melanoma patients targeting epigenetic modifiers |
| topic | epigenetics melanoma acetylation methylation combination therapy resistance |
| url | https://www.mdpi.com/2072-6694/13/24/6180 |
| work_keys_str_mv | AT mariagraciahernandez enhancingtherapeuticapproachesformelanomapatientstargetingepigeneticmodifiers AT zuleimamunoz enhancingtherapeuticapproachesformelanomapatientstargetingepigeneticmodifiers AT alejandrovillagra enhancingtherapeuticapproachesformelanomapatientstargetingepigeneticmodifiers |