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: |
|