دورية أكاديمية

Multi-omics analysis identifies repurposing bortezomib in the treatment of kidney-, nervous system-, and hematological cancers

التفاصيل البيبلوغرافية
العنوان: Multi-omics analysis identifies repurposing bortezomib in the treatment of kidney-, nervous system-, and hematological cancers
المؤلفون: Peter Larsson, Maxim Olsson, Sithumini Sarathchandra, Anna Fäldt Beding, Eva Forssell-Aronsson, Anikó Kovács, Per Karlsson, Khalil Helou, Toshima Z. Parris
المصدر: Scientific Reports, Vol 14, Iss 1, Pp 1-20 (2024)
بيانات النشر: Nature Portfolio, 2024.
سنة النشر: 2024
المجموعة: LCC:Medicine
LCC:Science
مصطلحات موضوعية: Drug repurposing, Proteasome inhibitor, Bortezomib, Gene expression profiling, Mutation profiling, Cancer, Medicine, Science
الوصف: Abstract Repurposing of FDA-approved drugs is a quick and cost-effective alternative to de novo drug development. Here, we identify genes involved in bortezomib sensitivity, predict cancer types that may benefit from treatment with bortezomib, and evaluate the mechanism-of-action of bortezomib in breast cancer (BT-474 and ZR-75–30), melanoma (A-375), and glioblastoma (A-172) cells in vitro. Cancer cell lines derived from cancers of the blood, kidney, nervous system, and skin were found to be significantly more sensitive to bortezomib than other organ systems. The in vitro studies confirmed that although bortezomib effectively inhibited the β5 catalytic site in all four cell lines, cell cycle arrest was only induced in G2/M phase and apoptosis in A-375 and A-172 after 24h. The genomic and transcriptomic analyses identified 33 genes (e.g. ALDH18A1, ATAD2) associated with bortezomib resistance. Taken together, we identified biomarkers predictive of bortezomib sensitivity and cancer types that might benefit from treatment with bortezomib.
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 2045-2322
Relation: https://doaj.org/toc/2045-2322
DOI: 10.1038/s41598-024-62339-x
URL الوصول: https://doaj.org/article/cb8556dc4f164843a07201a962a40d0f
رقم الأكسشن: edsdoj.b8556dc4f164843a07201a962a40d0f
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:20452322
DOI:10.1038/s41598-024-62339-x