Hedgehog/GLI signaling regulatory networks in colorectal cancer stem cells
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Agnese Po | Tutor di riferimento |
Colorectal cancer (CRC) is a heterogeneous disease with a complex biology and a wide number of genetic alterations. CRC is second leading cause of cancer death in Europe that affect widely women and men worldwide, this disease counts over 600000 of patients die every year. 5-year survival rate
The 5-year survival rate is related to tumour stage, moving from the 90% for stage I to only the 10% for IV stage. Current CRC treatment consists in surgery, targeted therapy, neoadjuvant radiotherapy and adjuvant chemotherapy.
Nonetheless drug-resistance often occur and is the most important challenge for CRC treatment, thus understanding molecular mechanisms driving resistance is an important asset for drug development.
I hypothesize that the subpopulation of colorectal cancer cells with stemness features, the colorectal cancer stem cells (CR-CSCs), together with an aberrant activation of the Hedgehog-GLI (HH-GLI) pathway are involved in CRC resistance to therapy. This proposal arises from my preliminary studies suggesting that HH-GLI signaling pathway has a role in CR-CSCs maintenance and, in this project, I aim to investigate whether HH-Gli and CR-CSCs are involved in the mechanisms underlying treatment resistance.