Periodic Reporting for period 1 - CONTACT (Cancer biOengineered Novel microTissues unrAveling Cancer plasTicity)
Reporting period: 2021-01-15 to 2023-01-14
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
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
• 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
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.