Cancer biOengineered Novel microTissues unrAveling Cancer plasTicity

Project Information

CONTACT

Grant agreement ID: 893129

DOI

10.3030/893129

Project terminated on 31 October 2022

EC signature date 6 April 2020

Start date 15 January 2021

End date 14 January 2023

Funded under

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Total cost

€ 171 473,28

EU contribution

€ 171 473,28

Coordinated by

FONDAZIONE ISTITUTO ITALIANO DI TECNOLOGIA
Italy

Periodic Reporting for period 1 - CONTACT (Cancer biOengineered Novel microTissues unrAveling Cancer plasTicity)

Reporting period: 2021-01-15 to 2023-01-14

Summary of the context and overall objectives of the project

Patients with triple negative breast cancer (TNBC) present a higher risk of recurrence and metastasis as existing chemotherapeutic strategies fail in nearly half of the cases. Recently, oncologists and researchers have started to focus their attention not only on cancer cells but also on their interactions with the microenvironment surrounding them. It is clear that the current methods of investigation are not able to grasp the complexity of these interactions. In vitro models that faithfully recapitulate the disease are urgently needed for the development of novel treatments. To address this, scientists of the EU-funded CONTACT project will develop a 3D bioengineered TNBC in vitro model that combines stromal components along with cancer cells. This tool will be useful in studying the mechanisms of interaction between cancer cells and their microenvironment as well as the reprogramming events triggering drug-tolerance. Long term, by using these models as a sort of patient’s avatar, it will become possible to establish patient-tailored treatment protocols based on combinatory therapy

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

The CONTACT project is articulated into three specific objectives of research (OR), corresponding to each Work Package (WP).
• OR1: Fabrication of Triple negative breast cancer microtissues (TNBC-µTs).
• OR2: Genomic characterization of the 3D TNBC-µTs.
• OR3: 3D TNBC-µTs as preclinical models for combinatorial therapy.
The novel in vitro tumor model will be challenged with neo-adjuvant chemotherapy drugs. The objective is to trigger drug-tolerance through transcriptional reprogramming in order to have a realistic model as tool to investigate the phenomena of drug resistance (WP1).
Recent evidence showed that non-coding RNAs have a role in transcriptional reprogramming. The objective is to detect potentially interesting non-coding RNAs that can be targeted or used as therapeutic agents to prevent or overcome therapeutic resistance (WP2).
The final objective is the study of a combinatorial chemotherapeutic approach based on conventional NACT protocol coupled with non-coding RNAs manipulation in order to improve the clinical outcome. Two miRNA candidates have been already identified by Nicassio’s team and will be tested here in combination with NACT using breast cancer microtissues

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

The project aims to understand the role of non-coding RNA in solid tumor. To do so, we used 3D in vitro models that can reduce and replace the use of animal as preclinical platform. This is a great advantage for the future and for the societal implications as required by the European directive.

3D in vitro model