Academic Journal

Androgen receptor is a determinant of melanoma targeted drug resistance.

التفاصيل البيبلوغرافية
العنوان: Androgen receptor is a determinant of melanoma targeted drug resistance.
المؤلفون: Samarkina, A., Youssef, M.K., Ostano, P., Ghosh, S., Ma, M., Tassone, B., Proust, T., Chiorino, G., Levesque, M.P., Goruppi, S., Dotto, G.P.
المصدر: Nature communications, vol. 14, no. 1, pp. 6498
سنة النشر: 2023
المجموعة: Université de Lausanne (UNIL): Serval - Serveur académique lausannois
مصطلحات موضوعية: Humans, Proto-Oncogene Proteins B-raf/metabolism, CD8-Positive T-Lymphocytes/metabolism, Receptors, Androgen/genetics, Drug Resistance, Neoplasm/genetics, Neoplasm Recurrence, Local/drug therapy, Melanoma/drug therapy, Melanoma/genetics, Melanoma/metabolism, Mitogen-Activated Protein Kinase Kinases, Carcinogenesis, Protein Kinase Inhibitors/pharmacology, Cell Line, Tumor
الوصف: Melanoma provides a primary benchmark for targeted drug therapy. Most melanomas with BRAF V600 mutations regress in response to BRAF/MEK inhibitors (BRAFi/MEKi). However, nearly all relapse within the first two years, and there is a connection between BRAFi/MEKi-resistance and poor response to immune checkpoint therapy. We reported that androgen receptor (AR) activity is required for melanoma cell proliferation and tumorigenesis. We show here that AR expression is markedly increased in BRAFi-resistant melanoma cells, and in sensitive cells soon after BRAFi exposure. Increased AR expression is sufficient to render melanoma cells BRAFi-resistant, eliciting transcriptional changes of BRAFi-resistant subpopulations, including elevated EGFR and SERPINE1 expression, of likely clinical significance. Inhibition of AR expression or activity blunts changes in gene expression and suppresses proliferation and tumorigenesis of BRAFi-resistant melanoma cells, promoting clusters of CD8 + T cells infiltration and cancer cells killing. Our findings point to targeting AR as possible co-therapeutical approach in melanoma treatment.
نوع الوثيقة: article in journal/newspaper
وصف الملف: application/pdf
اللغة: English
Relation: info:eu-repo/semantics/altIdentifier/pmid/37838724; info:eu-repo/semantics/altIdentifier/eissn/2041-1723; info:eu-repo/semantics/altIdentifier/urn/urn:nbn:ch:serval-BIB_CD9AA3E3CEE63; https://serval.unil.ch/notice/serval:BIB_CD9AA3E3CEE6; https://serval.unil.ch/resource/serval:BIB_CD9AA3E3CEE6.P001/REF.pdf
DOI: 10.1038/s41467-023-42239-w
الاتاحة: https://serval.unil.ch/notice/serval:BIB_CD9AA3E3CEE6
https://doi.org/10.1038/s41467-023-42239-w
https://serval.unil.ch/resource/serval:BIB_CD9AA3E3CEE6.P001/REF.pdf
http://nbn-resolving.org/urn/resolver.pl?urn=urn:nbn:ch:serval-BIB_CD9AA3E3CEE63
Rights: info:eu-repo/semantics/openAccess ; CC BY 4.0 ; https://creativecommons.org/licenses/by/4.0/
رقم الانضمام: edsbas.850ED3FD
قاعدة البيانات: BASE
الوصف
DOI:10.1038/s41467-023-42239-w