The Benefit of Reactivating p53 under MAPK Inhibition on the Efficacy of Radiotherapy in Melanoma.
V600EBRAF inhibition
intrinsic and acquired resistance
melanoma
p53 activation
radiotherapy
Journal
Cancers
ISSN: 2072-6694
Titre abrégé: Cancers (Basel)
Pays: Switzerland
ID NLM: 101526829
Informations de publication
Date de publication:
01 Aug 2019
01 Aug 2019
Historique:
received:
01
07
2019
revised:
25
07
2019
accepted:
30
07
2019
entrez:
4
8
2019
pubmed:
4
8
2019
medline:
4
8
2019
Statut:
epublish
Résumé
Radiotherapy (RT) in patients with melanoma historically showed suboptimal results, because the disease is often radioresistant due to various mechanisms such as scavenging free radicals by thiols, pigmentary machinery, or enhanced DNA repair. However, radiotherapy has been utilized as adjuvant therapy after the complete excision of primary melanoma and lymph nodes to reduce the rate of nodal recurrences in high-risk patients. The resistance of melanoma cells to radiotherapy may also be in relation with the constitutive activation of the MAPK pathway and/or with the inactivation of p53 observed in about 90% of melanomas. In this study, we aimed to assess the potential benefit of adding RT to BRAF-mutated melanoma cells under a combined p53 reactivation and MAPK inhibition in vitro and in a preclinical animal model. We found that the combination of BRAF inhibition (vemurafenib, which completely shuts down the MAPK pathway), together with p53 reactivation (PRIMA-1
Identifiants
pubmed: 31374895
pii: cancers11081093
doi: 10.3390/cancers11081093
pmc: PMC6721382
pii:
doi:
Types de publication
Journal Article
Langues
eng
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