Assessing the role of intratumoral microbiota in therapy responses using patient-derived tumor-on-chip

This action is part of the Cancer Mission cluster of projects on “Understanding (tumour-host interactions)"".Challenge: Primary or acquired resistance to therapies is a major challenge in oncology.

Recent research suggests that intratumoral microbiota may contribute to anti-cancer drug resistance, in particular to immunotherapies such as immune checkpoint inhibitors (ICI). However, experimental approaches to address the role of microbiota in human cancers are lacking.

Solution: Project ARTURO will ethically tackle this problem by using an innovative state-of-the-art 3D tumor-on-chip (ToC) model, as part of the emerging field of Micro-Physiological Systems (MPS).

Plan: The role of patient-derived bacteria, and of their postbiotics and released extra-cellular vesicles, in tumor ecosystem behaviors and drug responses, will be deciphered by integrating clinical data, omics analysis, and novel ToC-based information (by live imaging and single-cell transcriptomics).

The development of advanced computational methods to extract ToC-based information constitutes a major force and innovation in the field, with high potential to accelerate future applications of ToC technology in clinics.

The focus will be on two frequent poorly-understood cancer subtypes: non-small cell lung cancer (NSCLC) and invasive lobular breast cancer (ILC).

End-users’ perspectives will be addressed using a co-design approach to develop ethically sound and evidence-based cancer-related innovation and health policies.Impact: ARTURO results are expected to lead to a deep understanding of processes underpinning tumor-host interactions, helping to conceive novel microbiota-based intervention strategies, in particular for NSCLC and ILC patients.

ARTURO will take social, ethnical, cultural, and gender aspects into account, facilitating the translation of ARTURO's innovations to clinical practice and co-design of policies.

Ultimately, the ARTURO impacts will be far-reaching, contributing to future developments in cancer precision medicine and diagnostics and to the EU Mission – Cancer.