Description
Thyroid cancer is the most common endocrine malignancy, often driven by genetic alterations that activate the MAPK signaling pathway, leading to uncontrolled cell growth. Tyrosine kinase inhibitors (TKIs) are the best treatment option for advanced cases, but their effectiveness and toxicity vary significantly between patients due to differences in drug metabolism.
TKIs are primarily processed in the liver by cytochrome P450 (CYP) enzymes, which influence drug absorption and elimination. Genetic variations (polymorphisms) in metabolism-related genes can impact TKI bioavailability, efficacy, and side effects. However, little is known about these genetic factors in thyroid cancer patients, making treatment responses difficult to predict.
This project aims to optimize TKI therapy by investigating the relationship between genetic polymorphisms, drug levels, side effects, and microbiota alterations. Key objectives include:
TKIs are primarily processed in the liver by cytochrome P450 (CYP) enzymes, which influence drug absorption and elimination. Genetic variations (polymorphisms) in metabolism-related genes can impact TKI bioavailability, efficacy, and side effects. However, little is known about these genetic factors in thyroid cancer patients, making treatment responses difficult to predict.
This project aims to optimize TKI therapy by investigating the relationship between genetic polymorphisms, drug levels, side effects, and microbiota alterations. Key objectives include:
- Correlating clinical features with genetic profiles to understand individual drug responses.
- Examining plasma drug concentrations to link genetic variations with TKI side effects.
- Analyzing gut microbiota composition in patients experiencing severe diarrhea to explore potential links with drug metabolism.
- Developing personalized treatment strategies to improve therapeutic outcomes.
By integrating pharmacogenomics, drug monitoring, and microbiome analysis, this research will enhance treatment precision, minimize side effects, and maximize the clinical benefits of TKIs for thyroid cancer patients.
Collaborators
Università degli Studi di Perugia:
Dipartimento di Medicina e Chirurgia - Efisio Puxeddu, Sonia Moretti, Antonella Mencacci
External:
Università degli Studi di Siena - Maria Grazie Castagna (PI)
Università di Pisa - Rossella Elisei
Università degli Studi di Milano - Carla Colombo
Dipartimento di Medicina e Chirurgia - Efisio Puxeddu, Sonia Moretti, Antonella Mencacci
External:
Università degli Studi di Siena - Maria Grazie Castagna (PI)
Università di Pisa - Rossella Elisei
Università degli Studi di Milano - Carla Colombo
Funding
PRIN (Progetti di Ricerca di Rilevante Interesse Nazionale) – Bando 2022 PNRR