Illuminate the targetable kinome of chemotherapy-resistant triple negative breast cancer

Diplôme Master Illuminate the targetable kinome of chemotherapy-resistant triple negative breast cancer eng 2024-04-23 author Scapozza Alessandro 907367 director Coppé Jean-Philippe <p>Triple negative breast cancer (TNBC) represents one of the most aggressive types of breast cancer, characterized by a high rate of metastasis and poor prognosis. Due to the lack of HER- 2, progesterone receptor and estrogen receptor, targeted therapies remain largely ineffective. Chemotherapy remains the standard of care despite poor outcome caused by mechanisms of resistance. In the present project, a High-Throughput Kinase Activity Mapping was conducted on TNBC cell lines treated with a panel of chemotherapies. This revealed that the MAP3K8 kinase is hyperactivated upon exposure to chemotherapeutic stress. Next, cell lines were transduced to overexpress MAP3K8. MAP3K8 overexpression increased cell proliferation and resistance to chemotherapy. Finally, to tackle drug resistance, multiple drug combinations were tested, and some showed improved outcome compared to individual chemotherapy treatment, including when using MAP3K8 inhibitors. We hope that these results may lead to the design of effective drug combination and eventually improve TNBC patients’ survival.</p> Dewey 610 Dewey 615 Master II in Biomedical Sciences 15e8ae34-b37d-4a89-8780-712c2057749d Structure enseignement 206 31 Section des sciences pharmaceutiques 17 false 6b42bbed-f5b3-43ba-a9d3-0a3962f6ae8d Travaux d'étudiant-es en Sciences Biomédicales fee27519-910b-4032-b46a-62a931b8fffd Master thesis Restricted Scapozza_Alessandro_Research_intern.pdf 6068044 application/pdf edfc2fd02dd0fb60fee3191c2aba327aea2fd73e341bd20e17d7fd9d8cbe0354 restrictedAccess Faculté de médecine / Structure enseignement Faculté des sciences / Section des sciences pharmaceutiques

Title	Published in	Access level	OA Policy	Year	Views	Downloads

Illuminate the targetable kinome of chemotherapy-resistant triple negative breast cancer				2024	69	9

Archive ouverte UNIGE

Scapozza, Alessandro