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p53 activators<br />
ASPP Partner 5<br />
NFkappaB Partner 6<br />
Pin1 Partner 14<br />
HIPK2 Partner 14<br />
Chk1/Chk2 Partner 10<br />
JMY/Strap/p300 Partner 8<br />
Integrin avb3 Partner 13<br />
Aim<br />
The principal aim of this proposal is to ease both diagnosis<br />
and prognostic classifi cation, as well as the eff orts towards<br />
novel therapy regimens to treat patients suff ering from<br />
breast cancer and neuroblastoma. Overall, the integrated<br />
action of our consortium is aiming at re-establishing tumour<br />
suppressor activity in cancer, thereby translating basic<br />
knowledge of functional oncogenomics into cancer diagnoses<br />
and treatment, and contributing to leadership in<br />
European health technology.<br />
Expected results<br />
p53-homologues<br />
deltaNp73/p63 Partner 2<br />
p73/p63 ligands Partner 9<br />
p73, c-Abl, p300 Partner 11<br />
p73TA and YAP Partner 15<br />
Biotech SMEs<br />
genomics<br />
proteomics<br />
drug leads<br />
Clinical<br />
units<br />
patient data<br />
specimens<br />
therapy<br />
p53 activity and technology<br />
intrabodies Partner 15<br />
apoptosis Partner 4<br />
senescence Partner 7 V.R.<br />
DNA structure Partner 16<br />
DNA binding in vivo Partner 3, 15<br />
targets/regulators Partner 18, 1<br />
The overall goals of this integrated eff ort are to understand:<br />
• which modulators determine the tumour-suppressive<br />
activities of the p53 family members;<br />
• by what mechanisms these modulators aff ect the tumour<br />
suppression activities;<br />
• how the expression and activity of p53 modulators is<br />
regulated;<br />
• whether p53 modulators aff ect the biological characteristics<br />
of tumour cells;<br />
• whether the status of p53 modulators correlates with<br />
the clinical outcome and can be used to determine the<br />
individual prognosis;<br />
p53 inhibitors<br />
Mdm2 and p14Arf Partner 7<br />
Mdm2 and c-Abl Partner 3<br />
Mdmx Partner 12<br />
Mdm2 drug traget Partner 17,2<br />
Outline of the consortium.<br />
• whether and how p53 modulators can be targeted by<br />
therapeutic strategies, and be manipulated towards<br />
regaining tumour suppression;<br />
• disseminate the knowledge that will be produced to<br />
practically all the interested parties including medical<br />
doctors, and managerial staff in the industries;<br />
• familiarise SMEs with scientifi c research work and stateof-the<br />
art technology that will provide the necessary<br />
know-how for the improvement of their services and<br />
competitiveness.<br />
Potential applications<br />
The ultimate general objective of this research proposal is to<br />
provide a basis for the re-activation of tumour suppression<br />
and the design of novel therapeutic approaches to combat<br />
cancer. In particular, we are aiming at modulating p53 family<br />
activities to decrease resistance of tumour cells to anti-cancer<br />
treatments. Thus, the ultimate goal of this research proposal<br />
is the identifi cation of novel drug targets and strategies for<br />
induction of p53-mediated apoptosis in therapy-resistant<br />
cancer cells. The participation of the SMEs is expected to<br />
play a key role to the practical application of the knowledge<br />
that will be produced.<br />
BIOLOGY 11
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