Utilizing CD44v6 and V600EBRAF-mutation for in vitro targeted combination therapy of thyroid carcinomas.
Anaplastic thyroid cancer
BRAF
CD44v6
Combination therapy
Thyroid cancer
molecular radiotherapy
targeted therapy
Journal
Heliyon
ISSN: 2405-8440
Titre abrégé: Heliyon
Pays: England
ID NLM: 101672560
Informations de publication
Date de publication:
Dec 2023
Dec 2023
Historique:
received:
01
06
2023
revised:
07
11
2023
accepted:
15
11
2023
medline:
11
12
2023
pubmed:
11
12
2023
entrez:
11
12
2023
Statut:
epublish
Résumé
The aim of this study was to assess the feasibility of targeted therapy of thyroid carcinoma, first exploring potential targets BRAF, EGFR and CD44v6 in patient material through immunohistochemistry and mutation analysis. A patient cohort (n = 22) consisting of seven papillary (PTC), eight anaplastic (ATC) and seven follicular (FTC) thyroid carcinomas were evaluated. Additionally, eight thyroid carcinoma cells lines were analyzed for CD44v6-expression and sensitivity to the multi-kinase inhibitor sorafenib (Nexavar®), which targets numerous serine/threonine and tyrosine kinases, including the Raf family kinases. Targeted therapy using Of the two cell surface proteins, EGFR and CD44v6, the latter was overexpressed in >80 % of samples, while EGFR-expression levels were moderate at best in only a few samples. BRAF mutations were more common in PTC patient samples than in ATC samples, while FTC samples did not harbor BRAF mutations. CD44v6-expression levels in the thyroid carcinoma cell lines were more heterogenous compared to patient samples, while BRAF mutational status was in line with the original tumor type. Monotherapy in 3D multicellular ATC tumor spheroids with either This "proof of concept" targeted therapy study in the in vitro ATC 3D multicellular tumor spheroids indicated applicability of utilizing CD44v6 for molecular radiotherapy both as a monotherapy and in combination with sorafenib.
Identifiants
pubmed: 38076095
doi: 10.1016/j.heliyon.2023.e22594
pii: S2405-8440(23)09802-X
pmc: PMC10709381
doi:
Types de publication
Journal Article
Langues
eng
Pagination
e22594Informations de copyright
© 2023 The Authors.
Déclaration de conflit d'intérêts
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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