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- Mortensen, AnjaUppsala universitet,Cancerprecisionsmedicin,Science for Life Laboratory, SciLifeLab,Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden.;Rudbeck Lab, Dag Hammarskjolds Vag 20, S-75185 Uppsala, Sweden. (författare)
Utilizing CD44v6 and V600EBRAF-mutation for in vitro targeted combination therapy of thyroid carcinomas
- Artikel/kapitelEngelska2023
Förlag, utgivningsår, omfång ...
- Cell Press,2023
Nummerbeteckningar
- LIBRIS-ID:oai:gup.ub.gu.se/332585
- https://gup.ub.gu.se/publication/332585URI
- https://doi.org/10.1016/j.heliyon.2023.e22594DOI
- https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-519104URI
- http://kipublications.ki.se/Default.aspx?queryparsed=id:154433482URI
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- Språk:engelska
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- Aim: 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.Materials and methods: 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 (R)), which targets numerous serine/threonine and tyrosine kinases, including the Raf family kinases. Targeted therapy using 131I-AbN44v6, a novel anti-CD44v6 antibody, and/or sorafenib was evaluated in 3D multicellular tumor spheroids. RResults: 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 131I-AbN44v6 or sorafenib resulted in delayed spheroid growth. The combination of 131I-AbN44v6 and sorafenib was the most potent and resulted in significantly impaired spheroid growth.Conclusion: 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.
Ämnesord och genrebeteckningar
- MEDICIN OCH HÄLSOVETENSKAP Klinisk medicin Cancer och onkologi hsv//swe
- MEDICAL AND HEALTH SCIENCES Clinical Medicine Cancer and Oncology hsv//eng
- CD44v6
- BRAF
- Combination therapy
- Thyroid cancer
- Anaplastic thyroid cancer
- targeted therapy
- molecular radiotherapy
- CD44v6
Biuppslag (personer, institutioner, konferenser, titlar ...)
- Imgenberg-Kreuz, JulianaUppsala universitet,Reumatologi(Swepub:uu)julim920 (författare)
- Spiegelberg, Diana,1982-Uppsala universitet,Cancerprecisionsmedicin,Science for Life Laboratory, SciLifeLab,Öron-, näs- och halssjukdomar(Swepub:uu)diasp673 (författare)
- Botling, Johan,1964Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för laboratoriemedicin,Department of Laboratory Medicine,Univ Gothenburg, Inst Biomed, Dept Lab Med, Gothenburg, Sweden.(Swepub:gu)xbotlj (författare)
- Nestor, Marika,1976-Uppsala universitet,Science for Life Laboratory, SciLifeLab,Cancerprecisionsmedicin(Swepub:uu)manes424 (författare)
- Uppsala universitetCancerprecisionsmedicin (creator_code:org_t)
Sammanhörande titlar
- Ingår i:Heliyon: Cell Press9:122405-8440
Internetlänk
- https://doi.org/10.1016/j.heliyon.2023.e22594Fulltext
- https://uu.diva-portal.org/smash/get/diva2:1824216/FULLTEXT01.pdffulltext:print
- https://gup.ub.gu.se/publication/332585
- https://doi.org/10.1016/j.heliyon.2023.e22594
- https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-519104
- http://kipublications.ki.se/Default.aspx?queryparsed=id:154433482
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