دورية أكاديمية
Concurrent Inhibition of Akt and ERK Using TIC-10 Can Overcome Venetoclax Resistance in Mantle Cell Lymphoma
| العنوان: | Concurrent Inhibition of Akt and ERK Using TIC-10 Can Overcome Venetoclax Resistance in Mantle Cell Lymphoma |
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| المؤلفون: | Granau, Agnete Marie, Andersen, Pilar Aarøe, Jakobsen, Theresa, Taouxi, Konstantina, Dalila, Nawar, Mogensen, Johanne Bay, Kristensen, Lasse Sommer, Grønbæk, Kirsten, Dimopoulos, Konstantinos |
| المصدر: | Granau , A M , Andersen , P A , Jakobsen , T , Taouxi , K , Dalila , N , Mogensen , J B , Kristensen , L S , Grønbæk , K & Dimopoulos , K 2023 , ' Concurrent Inhibition of Akt and ERK Using TIC-10 Can Overcome Venetoclax Resistance in Mantle Cell Lymphoma ' , Cancers , vol. 15 , no. 2 , 510 . https://doi.org/10.3390/cancers15020510Test |
| سنة النشر: | 2023 |
| المجموعة: | Aarhus University: Research |
| مصطلحات موضوعية: | mantle cell lymphoma, PI3K/Akt, TIC-10, venetoclax |
| الوصف: | Venetoclax, a BCL-2 inhibitor, has proven to be effective in several hematological malignancies, including mantle cell lymphoma (MCL). However, development of venetoclax resistance is inevitable and understanding its underlying molecular mechanisms can optimize treatment response. We performed a thorough genetic, epigenetic and transcriptomic analysis of venetoclax-sensitive and resistant MCL cell lines, also evaluating the role of the stromal microenvironment using human and murine co-cultures. In our model, venetoclax resistance was associated with abrogated TP53 activity through an acquired mutation and transcriptional downregulation leading to a diminished apoptotic response. Venetoclax-resistant cells also exhibited an upregulation of the PI3K/Akt pathway, and pharmacological inhibition of Akt and ERK with TIC-10 led to cell death in all venetoclax-resistant cell lines. Overall, we highlight the importance of targeted therapies, such as TIC-10, against venetoclax resistance-related pathways, which might represent future therapeutic prospects. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.3390/cancers15020510 |
| الإتاحة: | https://doi.org/10.3390/cancers15020510Test https://pure.au.dk/portal/da/publications/concurrent-inhibition-of-akt-and-erk-using-tic10-can-overcome-venetoclax-resistance-in-mantle-cell-lymphomaTest(16edbeec-f3fe-4110-bc1d-b2ba30005032).html http://www.scopus.com/inward/record.url?scp=85146755999&partnerID=8YFLogxKTest |
| حقوق: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.7C8FC008 |
| قاعدة البيانات: | BASE |
| DOI: | 10.3390/cancers15020510 |
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