Cancer drug-induceed gastrointestinal toxicity: Pathogenesis and future management

This project is dedicated to investigate mechanisms underlying cancer drug-induced mucositis (CIM) and to identify targeted therapies for CIM.

We aim to gain a in-depth molecular understanding of how chemotherapeutics and protein kinase inhibitors affect the GI tract.

By elucidating these molecular effects, focusing on pathways such as ferroptosis, we seek to identify key signaling pathways involved in CIM pathogenesis. We will use clinically relevant preclinical animal models, selected for their translatability to clinics.

These models enable us to bridge the gap between bench and clinical practice, providing invaluable insights into CIM pathophysiology and guiding the development of effective interventions.

In particular, we are exploring the role of ferroptosis, a form of regulated cell death characterized by iron-dependent lipid peroxidation and membrane damage.

The association between ferroptosis and intestinal epithelial dysfunction (membrane and tight junctions) suggests its role in CIM pathogenesis.

Preliminary findings suggest that peroxidation-reactive lipids and statin drugs, may mitigate CIM severity by targeting ferroptosis and other processes. We will also use orally ingestible devices for assessing mucosal lesions and GI tract functions in patients. These devices and advanced imaging modalities, will gather data on mucosal integrity, strictures, and GI transit times.

This enables us to identify patients at risk for CIM and tailor interventions accordingly.