The I-SMART project aims to develop an innovative kit for a simplified and rapid molecular diagnostic test for minimally-invasive personalized oncological diagnosis of both clinical and archived (i.e., fresh or preserved) specimens.


Smart drugs are one of the basic elements of personalized cancer treatment. Due to the expression pattern of a few key genes, not all patients respond in the same manner to a particular therapy. In the course of this project, the partners plan to develop a minimally-invasive rapid test for a molecular level diagnosis that is capable of analyzing clinical specimens and detecting the expression of key genes or the presence of specific mutations that will characterize the patient's propensity to respond to treatment. 


The project intends to define a methodology capable of reducing the overall analysis time used to identify the key genes characterizing the patient's propensity to respond to treatment, and to develop a system useful for the molecular analysis of samples collected by a minimally-invasive method.


The project will make it possible to develop a non-invasive molecular diagnostic kit based on Real-Time polymerase chain reaction (PCR) technology. Starting with an appropriate clinical sample, the kit will make it possible to perform a quick and easy analysis of genome expression or mutation in the predictor genes that are indicative of the patient’s response to oncological therapy.


The application area for the I-SMART project is the in vitro diagnostics sector. The purpose of the I-SMART project is to develop an innovative kit for a simple, rapid and minimally-invasive molecular diagnostic test for personalized oncology diagnosis. 
The I-SMART kit is to be developed in a field that is characterized by its strongly innovative impetus, where a combination of "purely scientific" research, simplification of analytical procedures, and rapid development of diagnostic kits, are all key factors in the growth and evolution of clinical diagnosis.

Most healthcare systems today are affected by tight budgets, and it is therefore necessary to rationalize and reduce the costs of testing and diagnostic services.For this reason, while also mindful of the need to ensure maximum effectiveness in patient care, the diagnostic market is becoming increasingly important and competitive. In this context, the typing and identifying of the individual's genetic characteristics assumes a significant role in drug development, as it makes it possible for the therapies administered to reach new levels of efficacy.

In the oncology area, for example, the drugs on the market and those in the final phase of development are increasingly referenced to the preliminary identification of specific mutations or to genomic typing. This is due to the identification of molecular mechanisms that underlie the onset and possibly the progression of tumors.Fundamental to customized oncology medicine is the use of personalized therapies through the use of "smart drugs". However, in some circumstances, a particular therapy is not suitable for certain patients, who respond in an unexpected way due to their own mutational fingerprint or to the expression of a few key genes. Today, an essential element of oncological care is the identification of predictive genes that make it possible to identify in advance whether a particular patient will benefit from a particular therapy. Therefore, the environment in which in vitro diagnostic tests can be performed is affected by the increased demand for quick response tests. The most pressing need is to provide essential information rapidly to the treating physician (e.g. the oncologist) in order to ensure that the best therapy is made quickly available.

Breast cancer is the neoplastic disease most common in the female population, affecting one out of every nine women at some point in her life. In cases of breast cancer, the ability to diagnose the cancer in relation to its receptor and mutational structure is crucial for neo-adjuvant or preoperative therapy.

Usually the choice of a neo-adjuvant therapy is based on a diagnosis performed from a micro-biopsy (Tru-Cut) obtained by use of a larger-caliber cutting needle after an initial cytological sample has been taken from the patient through a fine-needle aspiration procedure.

The I-SMART project aims to develop a relatively non-invasive molecular diagnostic kit, based on Real-Time PCR technology, that is capable of performing a rapid, simple, cost-effective mutational and transcriptional analysis of responsive predictive genes from tumor samples that are either archived or freshly obtained.

The molecular diagnostic test developed by Alphagenics Biotech S.r.l. makes possible a significant reduction in diagnosis time and the costs sustained by simplifying the processing of clinical samples and the reading of the final results. Samples are analyzed and the results generated by use of dedicated software developed by Dotcom S.r.l.. The assay is based on the real-time amplification of locus-specific amplicons generated in a multiplex format using a molecular assay developed by Laboratorio Nazionale CIB (Area Science Park di Trieste).

A unique feature of this procedure is that it does not require nucleic acid purification (RNA, DNA), thanks to the simplification of the initial processing of the clinical sample through the use of a lysis solution, which makes it possible to obtain a raw lysis solution that is directly usable for the subsequent molecular analysis.
The method to be developed in the I-SMART project is intended to reduce the overall analysis time and to eliminate the possibility of losing valuable material during the purification of nucleic acids, as some of the initial clinical sample is usually lost during that process.

One of the aims of the I-SMART project is to set up the assay for use with specimens taken with fine-needle aspiration, currently used only for the preliminary cytological analysis. This procedure will allow the molecular analysis to be performed on relatively non-invasive samples (from fine-needle aspiration) instead of requiring a biopsy extraction with a larger-caliber needle (Tru-Cut micro biopsy). This will avoid the discomfort of this far more invasive methodology and ensure drastic reductions in both time and costs for the diagnosis.

Starting date: 04/18/2017

End date: 06/30/2018

Total project: € 474.121,50

Total grant: € 340.002,3