Tumours are composed by a heterogeneous cell population and even when the majority of the tumour mass can be destroyed by therapeutic interventions, the in vivo expansion of resistant tumour cells leads to disease relapse and death of the patients.
Tumour heterogeneity is the result of continuing somatic mutations and the outcome, mainly, of the aberrant differentiation of tumour stem cells (TSC), which are responsible of initiating tumour growth. Isolated tumour-initiating cells displayed biological features of stem cells, such as the ability of self-renew, ability to form non-adherent colonies when seeded at clonal density and to differentiate recapitulating the original tumour they were derived from.
In cancer cells the pathways of self-renewing are deregulated contributing to oncogenesis. Tumour stem cells have been recently identified in breast carcinoma. Our aim is to determine if TSC can be specifically targeted with new therapies since stem cells are the only ones responsible for the genesis of new metastasis.
Thus our research program will develop along four specific objectives:
- Isolation of putative TSC from breast carcinoma;
- Production and therapeutic use of monoclonal antibodies specific of TSC;
- Prognostic value of TSC evaluation;
- Evaluation of t he breast TSC genetic expression profile.
These studies will contribute to the identification of new therapeutic approaches not based on proliferation but on biomolecular features of stem cells.
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