Therapeutische Adressierung des PI3K/mTOR-Signalwegs in T-Zell-Lymphomen

Therapeutic Targeting of the PI3K/mTOR Signaling Pathway in T-Cell Lymphomas

by Lennart Hagen Thielking
Doctoral thesis
Date of Examination:2024-09-06
Date of issue:2024-09-02
Advisor:Prof. Dr. Gerald Wulf
Referee:Prof. Dr. Gerald Wulf
Referee:PD Dr. Dr. Lena Christin Conradi
Persistent Address: http://dx.doi.org/10.53846/goediss-10690

 

 

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Abstract

English

This dissertation focuses on investigating the relevance of the PI3K/mTOR signaling pathway in T-cell lymphomas. T-cell lymphomas still pose a therapeutic challenge in clinical hematology and are often associated with a poor prognosis, particularly in refractory or relapsed cases. The PI3K signaling pathway closely interacts with the mTOR pathway, and dysregulations have been observed in both pathways in T-cell lymphomas. They therefore present themselves as potential targets for new treatment strategies. The efficacy of various PI3K and mTOR inhibitors was examined in cell cultures. The results show that targeted inhibition of specific PI3K isoforms (particularly p110α and p110γ) in combination with mTOR inhibition leads to a promising suppression of cell proliferation in vitro. Additionally, the significance of inhibiting individual PI3K isoforms was examined, and potential resistance mechanisms, particularly through the restitution of the protein kinase pAKT, were investigated.
Keywords: T-Cell Lymphoma; PI3K/mTOR Pathway; Cancer Therapy; Hematology; Oncology; Signal Transduction; Cancer Research; Molecular Biology; Cell Culture; Pharmacology; Inhibitors; Drug Resistance; AKT; pAKT; Western Blot; Cell Proliferation; mTOR Inhibition; PI3K; Isoforms; mTOR
Schlagwörter: T-Zell-Lymphome; PI3K/mTOR-Signalweg; Krebstherapie; Hämatologie; Onkologie; Signaltransduktion; Krebsforschung; Molekularbiologie; Zellkultur; Pharmakologie; Inhibitoren; Medikamentenresistenz; AKT; pAKT; p110; Western Blot; Zellproliferation; mTOR-Inhibition; PI3K; Isoformen; mTOR
 
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