| Autor: |
Nupur Mukherjee, Alacoque Browne, Laura Ivers, Tapesh Santra, Mattia Cremona, Bryan T. Hennessy, Norma O’Donovan, John Crown, Walter Kolch, Dirk Fey, Alex J. Eustace |
| Jazyk: |
angličtina |
| Rok vydání: |
2022 |
| Předmět: |
|
| Zdroj: |
Journal of Personalized Medicine, Vol 12, Iss 8, p 1277 (2022) |
| Druh dokumentu: |
article |
| ISSN: |
2075-4426 |
| DOI: |
10.3390/jpm12081277 |
| Popis: |
Triple negative breast cancer (TNBC) remains a therapeutic challenge due to the lack of targetable genetic alterations and the frequent development of resistance to the standard cisplatin-based chemotherapies. Here, we have taken a systems biology approach to investigate kinase signal transduction networks that are involved in TNBC resistance to cisplatin. Treating a panel of cisplatin-sensitive and cisplatin-resistant TNBC cell lines with a panel of kinase inhibitors allowed us to reconstruct two kinase signalling networks that characterise sensitive and resistant cells. The analysis of these networks suggested that the activation of the PI3K/AKT signalling pathway is critical for cisplatin resistance. Experimental validation of the computational model predictions confirmed that TNBC cell lines with activated PI3K/AKT signalling are sensitive to combinations of cisplatin and PI3K/AKT pathway inhibitors. Thus, our results reveal a new therapeutic approach that is based on identifying targeted therapies that synergise with conventional chemotherapies. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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