Abstract
Thyroid cancer is the most common endocrine neoplasm worldwide, with a frequency of 12/100.000 new cases per year in Italy. Nowadays, Fine- Needle Aspiration Biopsy (FNAB) is the most common methodology used to establish the most adequate therapeutic approach, even though do not allow clinicians to define tumor aggressiveness. While associated to known molecular markers, FNAB still possess no predictive value towards therapeutic response (i.e. chemotherapeutics or biological drugs). The aim of this project is to develop a very innovative methodology to improve the management/treatment of patients with thyroid tumors.
This approach will be defined in this project in two phases:
- Step 1. First, in a pre-surgery stage, FNAB-obtained material will be used to evaluate both known tumor associated biomarkers and new molecular markers by using innovative technologies such as Methylated-RNA Immunoprecipitation (me-RIP) and Next Generation Sequencing (NGS). The me- RIP technology allows the evaluation of RNA methylation levels in order to define a specific profile for each tumor sample. Gathered data will help to decide whether to perform surgery or not, based on the aggressiveness characteristics.
- Step 2. Post-surgery, surgically removed material will be used to create three-dimensional cell cultures (organoids) deriving from a single tumor sample. This innovative technique will allow to evaluate tumor response to radioiodine and/or antineoplastic drugs treatments. Overall, this integrated approach will provide new predictive markers for personalized treatment of patients with thyroid tumors and, therefore, will be beneficial to improve the national healthcare system. In fact, it will allow to avoid unnecessary surgical procedures such as total thyroidectomy, i.e. for mildly aggressive thyroid tumors, and which leads to a deterioration in patients’ quality of life. From the development of this absolutely innovative method, the production of patents can also be derived.
Innovative features & competitive advantage
Major aim of this project is to develop an innovative integrated system to improve thyroid tumors management. Specifically, in a pre-surgical step, procedures planned in this project, based on NGS, will allow a better evaluation of tumor aggressiveness and will aid in suggest the type of surgical intervention required; post-surgery, the tumor response towards antineoplastic compounds will be analyzed with 3D cell cultures in order to select the most appropriate therapy for the single tumor sample. Therefore, the project is highly focused on “precision medicine”, which is based on the adaptability of the therapeutic approach to the patient-specific disease characteristics. The system here described is extremely innovative: in fact, in the pre-surgery stage, the analysis of RNA methylation will be evaluated as an innovative prognostic tool in thyroid cancer; moreover, post-surgery, the sensitivity towards antineoplastic drugs will be evaluated through the use of organoids. The development of this integrated system will allow to create an innovative approach potentially applicable to all the tumor types in which molecular markers definition is fundamental to discriminate both tumor aggressiveness and response to therapy.
Market sector & future commercial prospectives
This project will develop highly innovative approaches based on NGS technology for the identification of prognostic/predictive markers in thyroid cancer. Therefore, at the end of the project, several results will be achieved:
- Generation and validation of a low-cost NGS system to identify the presence of somatic mutations based on a panel of genes known to be involved in thyroid tumors progression.
- Evaluation of a very innovative approach (me-RIP), characterized by the analysis of RNA methylation patterns in neoplastic tissues and aimed to evaluate RNA methylation as a prognostic/predictive marker in thyroid cancer. To this purpose, new technologies meant to perform me-RIP on FNAB samples will be developed.
- Creation of a standardized workflow to create thyroid cancer 3D cultures (organoids) aimed to develop a methodology to evaluate tumor sensitivity towards antineoplastic drugs.
All obtained results would create an innovative pipeline for tumor management that could be offered to National Healthcare Services, as well as public and private Companies.