FRRB Project 3438215 - In depth analysis of salivary gland cancers: from cell lines and genomic evaluation towards clinical trials in locally advanced and recurrent/metastatic disease
The Coordinator of the project is ASST Spedali Civili di Brescia. The Lead Principal Investigator of the project is Prof. Cesare Piazza.
|Pathology:||High grade salivary gland cancers|
|Tematic Area:||Oncology - Rare Tumors|
|Project Start Date:||June 1, 2023|
|Project End Date:||May 31, 2026|
|Project Partners:|| - ASST Spedali Civili di Brescia
- Azienda Sociosanitaria Territoriale (ASST) dei Sette Laghi
- IRCCS Istituto Clinico Humanitas - Humanitas Mirasole S.p.A.
- Fondazione CNAO Centro Nazionale di Adroterapia Oncologica
High grade salivary gland cancers (SGCs), such as mucoepidermoid cancer, salivary duct cancer, high grade adenocarcinoma, carcinoma ex pleomorphic adenoma, carcinosarcoma, poorly differentiated carcinoma and adenoid cystic carcinoma (ACC), are rare tumors with very poor prognosis. The current treatment strategy includes surgical resection and postoperative photon radiotherapy (RT) as per risk factors; systemic therapy has a marginal role in view of the few drug options, their limited activity and high toxicity.
Our project is a translational, bench to bedside study aimed at investigating new treatment options and improving personalization of treatments.
The study plan includes 5 work packages:
1) Gene expression profiling (testing and validation) of a clinically annotated retrospective cohort to improve prognostic stratification and possibly define pathways to be tackled with new agents;
2) In vitro (cell lines) and in vivo (zebrafish model) pharmacological studies to test the activity of targeted agents and to provide the rationale for future phase 2 studies;
3) Radiosensitivity study of charged particles on cell lines to better understand radiobiology of SGCs and to create a more effective RT protocol;
4) Phase 2 clinical trial: simultaneous vs sequential boost in carbon ion RT in ACC (primary endpoint: toxicity);
5) Phase 2 clinical trials: cisplatin + targeted agents (PARP inh; CDK inh; HDAC inh) in recurrent/metastatic ACC not amenable to curative treatments (primary endpoint: response rate; historical comparison with lenvatinib).