Evolution of Acquired Drug Resistance in BRAF-Mutant Melanoma

Melanoma is a highly aggressive type of skin cancer. Metastatic melanoma tumors have historically featured a particularly poor prognosis and have often been considered incurable. Recent advances in targeted therapeutic interventions have radically changed the landscape in metastatic melanoma managem...

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Main Authors: Josué Ballesteros-Álvarez, Ana M. Blázquez-Medela
Format: Article
Language:English
Published: MDPI AG 2024-10-01
Series:DNA
Subjects:
Online Access:https://www.mdpi.com/2673-8856/4/4/25
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author Josué Ballesteros-Álvarez
Ana M. Blázquez-Medela
author_facet Josué Ballesteros-Álvarez
Ana M. Blázquez-Medela
author_sort Josué Ballesteros-Álvarez
collection DOAJ
description Melanoma is a highly aggressive type of skin cancer. Metastatic melanoma tumors have historically featured a particularly poor prognosis and have often been considered incurable. Recent advances in targeted therapeutic interventions have radically changed the landscape in metastatic melanoma management, significantly increasing the overall survival of patients. Hyperactive BRAF is the most common mutational event found in metastatic melanoma and its inhibition has proven to be a successful approach in a number of patients. Unfortunately, initial tumor retreat is followed by relapse in most cases, highlighting the elusiveness of finding a widely effective treatment. Melanoma tumors often carry a particularly high number of mutations in what is known as a high level of inter- and intra-patient tumor heterogeneity, driving resistance to treatment. The various mutations that are present in these tumors, in addition to impacting the root cause of the malignancy and the potential for therapeutic interventions, have also been known to arise during tumor clonal evolution leading to the establishment of drug resistance, a major issue in melanoma management.
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spelling doaj-art-d4e5c33b97264eb29d91f0534f1130412025-08-20T02:00:32ZengMDPI AGDNA2673-88562024-10-014435536910.3390/dna4040025Evolution of Acquired Drug Resistance in BRAF-Mutant MelanomaJosué Ballesteros-Álvarez0Ana M. Blázquez-Medela1Buck Institute for Research on Aging, Novato, CA 94945, USADepartment of Basic Medical Sciences, Western University of Health Sciences, Pomona, CA 91766, USAMelanoma is a highly aggressive type of skin cancer. Metastatic melanoma tumors have historically featured a particularly poor prognosis and have often been considered incurable. Recent advances in targeted therapeutic interventions have radically changed the landscape in metastatic melanoma management, significantly increasing the overall survival of patients. Hyperactive BRAF is the most common mutational event found in metastatic melanoma and its inhibition has proven to be a successful approach in a number of patients. Unfortunately, initial tumor retreat is followed by relapse in most cases, highlighting the elusiveness of finding a widely effective treatment. Melanoma tumors often carry a particularly high number of mutations in what is known as a high level of inter- and intra-patient tumor heterogeneity, driving resistance to treatment. The various mutations that are present in these tumors, in addition to impacting the root cause of the malignancy and the potential for therapeutic interventions, have also been known to arise during tumor clonal evolution leading to the establishment of drug resistance, a major issue in melanoma management.https://www.mdpi.com/2673-8856/4/4/25melanomadrug resistancemutationtumor clonal evolutionBRAFMITF
spellingShingle Josué Ballesteros-Álvarez
Ana M. Blázquez-Medela
Evolution of Acquired Drug Resistance in BRAF-Mutant Melanoma
DNA
melanoma
drug resistance
mutation
tumor clonal evolution
BRAF
MITF
title Evolution of Acquired Drug Resistance in BRAF-Mutant Melanoma
title_full Evolution of Acquired Drug Resistance in BRAF-Mutant Melanoma
title_fullStr Evolution of Acquired Drug Resistance in BRAF-Mutant Melanoma
title_full_unstemmed Evolution of Acquired Drug Resistance in BRAF-Mutant Melanoma
title_short Evolution of Acquired Drug Resistance in BRAF-Mutant Melanoma
title_sort evolution of acquired drug resistance in braf mutant melanoma
topic melanoma
drug resistance
mutation
tumor clonal evolution
BRAF
MITF
url https://www.mdpi.com/2673-8856/4/4/25
work_keys_str_mv AT josueballesterosalvarez evolutionofacquireddrugresistanceinbrafmutantmelanoma
AT anamblazquezmedela evolutionofacquireddrugresistanceinbrafmutantmelanoma