Targeting Genome Stability in Melanoma—A New Approach to an Old Field
Despite recent groundbreaking advances in the treatment of cutaneous melanoma, it remains one of the most treatment-resistant malignancies. Due to resistance to conventional chemotherapy, the therapeutic focus has shifted away from aiming at melanoma genome stability in favor of molecularly targeted...
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doaj-42905ce04ff9444b94ac56b40f3d716b2021-03-28T23:00:16ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-03-01223485348510.3390/ijms22073485Targeting Genome Stability in Melanoma—A New Approach to an Old FieldMarta Osrodek0Michal Wozniak1Department of Molecular Biology of Cancer, Medical University of Lodz, 92-215 Lodz, PolandDepartment of Molecular Biology of Cancer, Medical University of Lodz, 92-215 Lodz, PolandDespite recent groundbreaking advances in the treatment of cutaneous melanoma, it remains one of the most treatment-resistant malignancies. Due to resistance to conventional chemotherapy, the therapeutic focus has shifted away from aiming at melanoma genome stability in favor of molecularly targeted therapies. Inhibitors of the RAS/RAF/MEK/ERK (MAPK) pathway significantly slow disease progression. However, long-term clinical benefit is rare due to rapid development of drug resistance. In contrast, immune checkpoint inhibitors provide exceptionally durable responses, but only in a limited number of patients. It has been increasingly recognized that melanoma cells rely on efficient DNA repair for survival upon drug treatment, and that genome instability increases the efficacy of both MAPK inhibitors and immunotherapy. In this review, we discuss recent developments in the field of melanoma research which indicate that targeting genome stability of melanoma cells may serve as a powerful strategy to maximize the efficacy of currently available therapeutics.https://www.mdpi.com/1422-0067/22/7/3485melanomatargeted therapyMAPK inhibitorsimmune checkpoint inhibitorsdrug resistanceDNA damage |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Marta Osrodek Michal Wozniak |
spellingShingle |
Marta Osrodek Michal Wozniak Targeting Genome Stability in Melanoma—A New Approach to an Old Field International Journal of Molecular Sciences melanoma targeted therapy MAPK inhibitors immune checkpoint inhibitors drug resistance DNA damage |
author_facet |
Marta Osrodek Michal Wozniak |
author_sort |
Marta Osrodek |
title |
Targeting Genome Stability in Melanoma—A New Approach to an Old Field |
title_short |
Targeting Genome Stability in Melanoma—A New Approach to an Old Field |
title_full |
Targeting Genome Stability in Melanoma—A New Approach to an Old Field |
title_fullStr |
Targeting Genome Stability in Melanoma—A New Approach to an Old Field |
title_full_unstemmed |
Targeting Genome Stability in Melanoma—A New Approach to an Old Field |
title_sort |
targeting genome stability in melanoma—a new approach to an old field |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1661-6596 1422-0067 |
publishDate |
2021-03-01 |
description |
Despite recent groundbreaking advances in the treatment of cutaneous melanoma, it remains one of the most treatment-resistant malignancies. Due to resistance to conventional chemotherapy, the therapeutic focus has shifted away from aiming at melanoma genome stability in favor of molecularly targeted therapies. Inhibitors of the RAS/RAF/MEK/ERK (MAPK) pathway significantly slow disease progression. However, long-term clinical benefit is rare due to rapid development of drug resistance. In contrast, immune checkpoint inhibitors provide exceptionally durable responses, but only in a limited number of patients. It has been increasingly recognized that melanoma cells rely on efficient DNA repair for survival upon drug treatment, and that genome instability increases the efficacy of both MAPK inhibitors and immunotherapy. In this review, we discuss recent developments in the field of melanoma research which indicate that targeting genome stability of melanoma cells may serve as a powerful strategy to maximize the efficacy of currently available therapeutics. |
topic |
melanoma targeted therapy MAPK inhibitors immune checkpoint inhibitors drug resistance DNA damage |
url |
https://www.mdpi.com/1422-0067/22/7/3485 |
work_keys_str_mv |
AT martaosrodek targetinggenomestabilityinmelanomaanewapproachtoanoldfield AT michalwozniak targetinggenomestabilityinmelanomaanewapproachtoanoldfield |
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1724199376791797760 |