Project description
A bioengineered model for investigating plasticity in triple negative breast cancer
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.
Objective
Triple Negative Breast Cancer is the most aggressive among breast cancer subtypes. The conventional neo-adjuvant therapy is ineffective in about 50% of cases, with patients presenting a higher risk of recurrence and metastasis. The failure of the currently available chemotherapeutic strategy is also due to the lack of cancer preclinical models that are “close-to-reality” and therefore able to accurately recapitulate the tumor microenvironment, the transcriptional reprogramming and the cancer cells plasticity of patients with poor outcomes. Currently, miRNAs and lncRNAs are believed to be key components in all major adaptation pathways and involved in the transcriptional reprogramming that occurs after TNBC treatment with neo-adjuvant therapy. Moreover, bioengineered preclinical in vitro models permit to study the molecular mechanisms underpinning adaptive responses to chemotherapy by selecting transcriptional phenotypes that somehow make tumor cells tolerant to drugs, without requiring a selection of genetic features.
The CONTACT project aims at developing a 3D bioengineered TNBC in vitro model able to shed light on the mechanisms of tumor cells reprogramming that trigger drug-tolerance. The model will include stromal components along with cancer cells and represent an important tool in studying the role of the stroma in transcriptional reprogramming. Bioengineered 3D breast cancer in vitro models will accelerate the establishment of personalized treatment protocols that take into account what exactly, in each patient, leads to transcriptional reprogramming. The CONTACT project will boost the scientific career of the experienced researcher and will lead her to an independent role in research. The project will also broad the expertise of the experienced researcher in the area of cancer genomics. Her expertise in 3D tumor models will pave the way for a new research line in the scientific portfolio of the host institution.
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Funding Scheme
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)Coordinator
16163 Genova
Italy