Programma MD-PhD della Scuola di Medicina

Cancer stem cells as therapeutical targets. Responsabile prof Carla Boccaccio

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Programma

Increasing evidence shows that tumours are structured according to a hierarchy that includes two main components: (i) at the apex, a (tiny) subset of cancer stem cells (CSCs) that retain unrestricted proliferative ability (self-renewal), and continuously regenerate or add to the tumour; (ii) at the base, a large subset of cells that, unlike CSCs, retain restricted proliferative ability, and undergo aberrant differentiation. This hierarchical model implies that CSCs must be eradicated in order to cure the tumour. The task is challenging, as CSCs are often resistant to therapies (including targeted drugs) otherwise effective against the remaining cancer cells, and can be responsible for cancer relapse in apparently cured patients. In order to envisage more effective therapeutical strategies, we
aim to investigate the genetic and molecular mechanisms that account for CSC sensitivity or resistance to conventional radio- and chemo-therapy, or innovative oncogene-targeted therapies.
A mechanism of CSC resistance is activation of MET, the oncogene encoding the tyrosine kinase receptor for HGF, which controls invasive growth in either physiological (embryo development and tissue regeneration) or pathological (cancer) conditions. In CSCs derived from colorectal cancer, glioblastoma, and other tumours, we are studying whether the MET oncogene mediates resistance to irradiation and other DNA-damaging agents. Moreover, as MET drives invasive growth, we are studying whether it controls the CSC ability to self-renew and disseminate. We are then testing whether specific small-molecule kinase inhibitors and monoclonal antibodies targeting MET, alone or combined with radio- and chemo-therapy, can be exploited to eradicate CSCs.

Attività di supporto

Collaboratori: Francesca De Bacco

Note

• Progetto del corso: Cellule staminali e medicina rigenerativa
• Qualificazione scientifica del coordinatore: Pubblicazioni della prof. Boccaccio su PubMed
• Struttura in cui si svolge attività di ricerca: Laboratory of Cancer Stem Cell Research at the IRCC-Institute for Cancer Research, Str. Prov. 142, 10060 Candiolo, Torino

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