Thesis, COLLÉGIALITÉ
Hemmer, Marine
Promotor(s) : Nokin, Marie-Julie
Date of defense : 2-Jul-2024 • Permalink : http://hdl.handle.net/2268.2/20513
Details
Title : | Thesis, COLLÉGIALITÉ |
Author : | Hemmer, Marine |
Date of defense : | 2-Jul-2024 |
Advisor(s) : | Nokin, Marie-Julie |
Committee's member(s) : | Bellahcene, Akeila
Blomme, Arnaud Deroanne, Christophe |
Language : | English |
Keywords : | [en] Resistance, targeted therapies, melanoma, metabolism |
Discipline(s) : | Human health sciences > Oncology |
Institution(s) : | Université de Liège, Liège, Belgique |
Degree: | Master en sciences biomédicales, à finalité approfondie |
Faculty: | Master thesis of the Faculté de Médecine |
Abstract
[en] The V600E mutation of the BRAF gene, involved in the MAP kinase pathway, is present in many cancers, including melanoma. Patients with this type of cancer are treated with targeted therapy combining Dabrafenib, acting specifically on the mutated form of BRAF, and Trametinib, targeting downstream MEK. Unfortunately, this approach rapidly leads to the development of acquired resistance. Persistent, treatment-tolerant cells are seen as the reservoir from which genetically resistant cells subsequently emerge, making tolerant cells a more effective therapeutic target than genetically resistant cells. Our hypothesis is that, by becoming persistent, cancer cells adapt their energetic metabolism and acquire potential therapeutically targetable vulnerabilities. The aim of this work is therefore to identify the energetic modifications developed by these persistent cells under the pressure of targeted therapy. Mitochondrial activity, quantity and localization were assessed using Seahorse flux analyzer, flow cytometry and confocal microscopy, respectively. Expression levels of various enzymes and transporters involved in glycolysis and mitochondrial activity were quantified using western blot and qPCR. Our results revealed increased mitochondrial activity in some persistent cells compared with their own parental cells. However, some discrepancies have been observed when deciphering further the expression levels of key metabolic players. Future investigations are required to better elucidate the metabolic adaptations of persister cells and identify specific targetable vulnerabilities.
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