Ricerc@Sapienza

Colorectal cancer (CRC) is a heterogeneous disease with a complex biology and a wide number of altered genes. Advances with new targeted therapies have been achieved and available options for treating CRC patients have prolonged patient's survival. Drugs specific for driven mutations are already available in clinical settings; nonetheless CRC has the ability to develop resistance. Additionally, some patients do not have to date any specific targeted therapy necessitating further research and treatment development.
Hedgehog-GLI (HH-GLI) pathway is a potent morphogen and master regulator of stem/progenitor cells, specifically dysregulated in different types of tumors (e.g. colon, brain and lung).
We hypothesize that the subpopulation of colorectal cancer cells with stemness, the colorectal cancer stem cells (CR-CSCs), together with the aberrant HH-GLI signaling are involved in CRC resistance to therapy. This project is based on preliminary studies suggesting that HH-GLI activation has a function in CR-CSCs maintenance and the aim of this proposal is to investigate whether HH-GLI is involved in the mechanisms underlying treatment resistance.
The project specifically addresses three strategic issues:
1. Providing data on patterns of HH-GLI pathway components expression among CR-CSCs carrying different mutations.
2. Investigation the function of GLI1, transcription activator of HH-GLI, in controlling CR-CSCs behavior and resistance to therapy.
3. Study of the effects of GLI1 inhibition in vitro.
The project aims to identify promising molecular target candidates that could be ultimately used to design personalized safe and effective treatments on the basis of each patient's features to improve the efficacy of therapy.