Summary The work described in this thesis focuses on the characterization of the mechanism(s) underlying the deregulated activation of the intrinsic or mitochondrial apoptotic pathway in non-small cell lung cancer (NSCLC) cells. Apoptosis suppression might contribute to the chemoresistance often observed in NSCLC patients, and elucidation of the molecular causes of this resistance may provide clues for the development of targeted apoptosis-based therapies. In this introduction, lung cancer and current treatment regimens are described, and mechanisms responsible for chemoresistance, in particular towards cisplatin, are summarized. Furthermore, the major apoptotic pathways are presented, with a detailed description of the mitochondrial apoptotic route and its regulation by Bcl-2 family members and inhibitors of apoptosis. Finally, known mechanisms of apoptosis-dependent chemoresistance and innovative apoptosis-targeting strategies for cancer therapy are discussed.Giaccone, G. [Promotor
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