Cancer Research for Children
Project location: ITALY
Project start date: January 2005 - Project end date: This project covers various years
Project number: 2005-13
Beneficiary: AIRC - Associazione Italiana per la Ricerca sul Cancro
Grant Extension for the Comprehensive Diagnosis and Treatment Research on Intracranial Paediatric Ependymoma in Italy
Some guidelines driven from this national Italian protocol will become the backbone of a European protocol scientifically sponsored by SIOP (International Society of Paediatric Oncology) for all children older than one year: radiation technique both for patients without and with tumor residue after surgery and the chemotherapy schedule that will be randomized after radiation for all patients will follow Italian experience. It is evident that pre-clinical studies have not had much to offer so far for everyday patient care. For this reason, relevant information will be retrieved from a uniform analysis of a larger number of cases than those of the first interregional project previously stored by the participating institutions. This approach has the potential to:
• identify relevant disease subgroups, separated by differential genomic signatures for patient stratification purposes;
• correlate the patient response to chemotherapy and radiotherapy with specific molecular features, in order to help interpreting the trial results;
• prospectively identify molecular markers that are valid surrogates of response to treatment;
• guide the use of chemotherapeutics and differential activated oncogenic pathways signatures;
• guide choices in the window phase for patients with residual disease after surgery and in the offlabel targeted treatments for relapsing patients.
The objective of next the 2 years of activity of the plan is to complete the clinical study in course and to identify at the level of the DNA which other alterations can be useful like specific targets. At the international level, the results of the study will be published on the most important scientific journals. The results will also be disseminated on all Italian media and our magazine "Fondamentale". Moreover, the availability of new therapeutical approaches at the most important oncologic pediatric Institutions, that will have taken part to the study, will disseminate the results by itself, through word-of-mouth, all over the Country.
AIRC will keep sustaining the project financially with the funds raised yearly through various AIRC fund-raisng activities and events.
The project will be realized in Italy in the following research institutions: Ist.Nazionale Neurologico "C.Besta" - MILANO, Ospedale Infantile Regina Margherita - TORINO, Ist.Giannina Gaslini - GENOVA, Ospedale Pediatrico A. Meyer - FIRENZE, Università di Roma "La Sapienza" - ROMA, Fondazione IRCCS Istituto Nazionale dei Tumori - MILANO, IRCCS Eugenio Medea - BOSISIO PARINI (LC).
Grant Extension for the Inter-Regional Paediatric Cancer Research Project on Medulloblastoma in Italy
The recent advances in understanding the pathogenesis of MB led to a more detailed picture of the MB genetics, nonetheless the specific genetic alteration involved in the majority of these neoplasms are still uncertain. So far the main limitation of the current treatment is the lack of specificity. In the first 3 years of work, researchers identify a chromosome alterations which is correlated with the turn aggressive. This alteration could be a specific target for developing new therapeutic approaches. AIRC will perform studies focused on the identification of MB "stem cells", to deeply under stand their biology and address an important question on how to impair their dormancy properties and their niche formation for future terapies. Then one approach will deal with drug discoveries, which will make use of a new library of compounds both synthetic and naturals which will screen on MB cell lines for their efficacy and inhibition of the most signaling activated pathways to slow down tumorigenesis. A second approach will use synthetic nucleic acid derivatives (PNA) and siRNAs to impair tumorigenesis driven by candidate genes belonging to the SHH, WNT, Notch pathways and other main pathways involved in MB.
The principal achievement will be to contribute to the molecular basis of MB, and to design pathway oriented therapies, to increase the success of patient's treatment. At the international level, the results of the study will be published on the most important scientific journals. The results will also be disseminated on all Italian media and AIRC magazine "Fondamentale". Moreover, the availability of new therapeutical approaches at the most important oncologic pediatric Institutions, that will have taken part to the study, will disseminate the results by itself, through word-of-mouth, all over the Country. AIRC will keep sustaining the project financially with the funds raised yearly through various AIRC fund-rasing activities and events.