Gastrointestinal Cancer

Francesco Leone, M.D.
Assistant Professor
University of Torino School of Medicine
E-mail: francesco.leone@ircc.it
Phone. +39.011.9933503 - 3250
Fax. +39.011.9933524/3275


Publications
Francesco Leone
Research topic:
New strategies in advanced biliary cancer treatment

Background:
Biliary tract cancer (BTC) is a rare and lethal disease with very few therapeutic options. Previous studies suggest that Epithelial Growth Factor Receptor (EGFR) pathway activation could be involved in BTC pathogenesis, envisaging a potential role of anti-EGFR monoclonal antibodies.

Research achievements:
Despite encouraging early evidence of a major involvement of EGFR pathway in BTC, targeted anti-EGFR therapy has proven disappointing in the clinic, and resistance seems to involve mechanisms other than RAS mutations. Our group has coordinated a multicenter randomized Phase II clinical trial (Vecti-BIL study) to evaluate the effectiveness of Panitumumab (P) in combination with chemotherapy in patients with advanced BTC selected for the absence of KRAS mutations on exon 2. Patients were randomized to receive the combination of P with gemcitabine and oxaliplatin (GEMOX) or GEMOX alone. The addition of P did not result in a statistically significant improvement in progression-free survival (PFS) (5.3 months vs 4.4 months of GEMOX alone; log-rank test, p= .27) and had no impact on overall survival (OS, 9.9 months with P-GEMOX vs 10.2 months with GEMOX; p= .42). Even restricting survival analyses to all RAS and BRAF wild-type patients, no statistically significant differences in PFS or OS were found between treatment arms.Resistance to chemo/targeted treatments may be explained through alternative pathway activation or the presence of a stem cell compartment. Comprehensive molecular profiling and genetic analyses of the last 10 years have provided considerable advances in the identification of druggable targets in BTC. In our preclinical experience, we explored alternative molecules such as ET-743 and the Src inhibitor Saracatinib. Moreover, we demonstrated that 9% of patients harbor the FIGROS1 rearrangement, in a case series of Italian patients with BTC, suggesting that inhibition of ROS1 may have important clinical implications.To test new anticancer treatments in BTC we established a human intrahepatic cholangiocarcinoma cell line derived from an Italian patient and a patient-derived intrahepatic cholangiocarcinoma xenograft model.

Conclusions and perspectives:
Molecular profiling has outlined complex oncogenic pathway alterations in BTC including ERBB2, RAS-RAFMEK, PI3K-AKT-mTOR, JAK/STAT, andIDH1/2. Gene fusions involving ROS1 and FGFR2 represent timely druggable alterations. These findings are expected to provide important implications for developing future therapies in BTC.

Gastrointestinal Cancer - Staff

Phone: 011.993.3503
Email: giuliana.cavalloni@ircc.it
Phone: 011.993.3628
Email: federica.colombi@ircc.it
Phone: 011.993.3628
Email: francesca.davanzo@ircc.it
Phone: 011.993.3628
Email: ilaria.depretis@ircc.it
Phone: 011.993.3628
Email: elisabetta.fenocchio@ircc.it
Phone: 011.993.3628
Email: roberto.filippi@ircc.it
Phone: 011.993.3628
Email: donatella.marino@ircc.it
Phone: 011.993.3503
Email: caterina.peraldoneia@ircc.it

Contacts

Istituto di Candiolo
Strada Provinciale, 142 km 3,95
10060 Candiolo, Torino-Italy

CENTRALINO
011-9933.111

How to reach the Institute

Visualizza IRCC in una mappa di dimensioni maggiori

Support Us