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p53 Family in Resistance to Targeted Therapy of Melanoma

Vlašić, Ignacija; Horvat, Anđela; Tadijan, Ana; Slade, Neda (2023) p53 Family in Resistance to Targeted Therapy of Melanoma. International Journal of Molecular Sciences, 24 (1). ISSN 1422-0067

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Metastatic melanoma is one of the most aggressive tumors, with frequent mutations affecting components of the MAPK pathway, mainly protein kinase BRAF. Despite promising initial response to BRAF inhibitors, melanoma progresses due to development of resistance. In addition to frequent reactivation of MAPK or activation of PI3K/AKT signaling pathways, recently, the p53 pathway has been shown to contribute to acquired resistance to targeted MAPK inhibitor therapy. Canonical tumor suppressor p53 is inactivated in melanoma by diverse mechanisms. The TP53 gene and two other family members, TP63 and TP73, encode numerous protein isoforms that exhibit diverse functions during tumorigenesis. The p53 family isoforms can be produced by usage of alternative promoters and/or splicing on the C- and N-terminus. Various p53 family isoforms are expressed in melanoma cell lines and tumor samples, and several of them have already shown to have specific functions in melanoma, affecting proliferation, survival, metastatic potential, invasion, migration, and response to therapy. Of special interest are p53 family isoforms with increased expression and direct involvement in acquired resistance to MAPK inhibitors in melanoma cells, implying that modulating their expression or targeting their functional pathways could be a potential therapeutic strategy to overcome resistance to MAPK inhibitors in melanoma.

Item Type: Article
Uncontrolled Keywords: melanoma ; MAPK inhibitors ; resistance ; p53 ; p63 ; p73 ; p53 family isoforms
Subjects: BIOMEDICINE AND HEALTHCARE > Basic Medical Sciences
Divisions: Division of Molecular Medicine
Project titleProject leaderProject codeProject type
Otkrivanje novih proteinskih interakcija kao podloga za nove pristupe liječenju melanoma čovjekaSlade, NedaIP-2013-11-1615HRZZ
Depositing User: Ignacija Vlašić
Date Deposited: 16 Jun 2023 10:18
DOI: 10.3390/ijms24010065

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