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Molecular mechanisms of programmed cell death (apoptosis) and the development of apoptosis resistance in tumors

Objective

Cancer is still one of the most common causes of death in Europe and any treatments to avoid or alleviate health risk associated with cancer bears the potential to significantly ameliorate the health of the European population. A major rationale in current cancer therapy is based on the understanding that virtually all cells in higher organisms posses a cellular suicide program referred to as apoptosis. Under physiological circumstances, apoptosis is induced as a developmental program or, more frequently, as a consequence of environmental insult. In the latter instance, apoptosis is probably the single most important tumor suppressor mechanism in mammals. Cancer therapy has long relied on empirically derived cytotoxic treatments that are now recognized as relatively unspecific ways to induce cell death, with a certain preference for cancer cells and rapidly proliferating cells. A major clinical problem, of considerable practical importance, is the development of resistance to cytotoxic cancer drugs. From our current perspective, resistance to cytotoxic cancer drugs can be largely explained by the development of resistance to apoptosis. To resolve this problem, the project will study the following key questions:
1. What determines the selective apoptotic killing of tumor cells by anticancer agents?
2. Which molecular alterations underlie the development of apoptosis resistance in tumor cells and how can these alterations be reversed by specific treatments? In order to develop new strategies for the diagnosis and new therapeutic approaches for the treatment of apoptosis-resistant tumors, the pathways triggering apoptosis in various cell types will be addressed by a detailed analysis of the signaling pathways in various human tissues. We also propose to study the role of various cellular genes and mutations in these genes for the execution of the apoptotic response. A particular aspect of the current program is the use of genome-wide approaches

Funding Scheme

NET - Research network contracts

Coordinator

AUSTRIAN ACADEMY OF SCIENCES
Address
Rennweg 10
A - 6020 Innsbruck
Austria

Participants (5)

CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE
France
Address
Route De Mende 1919
34293 Montpellier
GERMAN CANCER RESEARCH CENTER
Germany
Address
Im Neuenheimer Feld 280
69120 Heidelberg
KAROLINSKA INSTITUTE
Sweden
Address
Karolinska Hospital
171 76 Stockholm
THE PROVOST, FELLOWS AND SCHOLARS OF THE COLLEGE OF THE HOLY AND UNDIVIDED TRINITY OF QUEEN ELIZABETH NEAR DUBLIN HEREINAFTER TRINITY COLLEGE DUBLIN
Ireland
Address
St James's Hospital, James's Street
8 Dublin
UNIVERSITAETSKLINIKUM CHARITE - MEDIZINISCHE FAKULTAET DER HUMBOLDT-UNIVERSITAET ZU BERLIN
Germany
Address
Lindenberger Weg 80
13125 Berlin