Triple Negative Breast cancer control of the immune tumour microenvironment in metastasis

        Metastasis, the spread of cancer to secondary organs, accounts for approximately 90% of cancer-related deaths mainly due to resistance to conventional treatments and organ failure. Unfortunately, our understanding of metastasis evolution, from its onset to treatment resistance, remains limited. Although natural selection acts on phenotypes, cancer research has traditionally focused on genotype alterations. Despite extensive efforts, specific genetic alterations that would confer metastatic functions have not yet been identified. In addition, the regulation of a cell´s phenotypic output is multi-layered, with both transcriptional and epigenetic mechanisms playing key roles. To address these crucial gaps in knowledge, we have established the ADAPTMET consortium. The goal of the consortium is to bolster basic research on metastatic cancers, ultimately influencing drug development and improving the clinical standard of care. This initiative aligns with the solution-oriented missions of Horizon Europe, with cancer being one of its priority areas.

        Cytoskeletal dynamics are crucial during the complex processes that take care during metastatic dissemination. As part of the consortium, in this project at ICR, we will explore the role of the cytoskeleton in controlling Triple Negative Breast Cancer (TNBC). We will investigate how the actomyosin cytoskeleton is important for educating the immune tumour microenvironment (iTME) during metastatic organ colonisation and outgrowth. We will find commonalities and differences between lung and brain metastasis. 3D co-culture systems and organoids, mouse models and patient samples will be used to dissect the specific crosstalk between cancer cells and the TME supporting their metastatic abilities.

         Specifically, the student will investigate how Myosin II dynamics regulates the metastatic iTME. The student will explore how these mechanisms operate in early vs late metastasis to identify therapeutic vulnerabilities of TNBC cells. We will leverage our access to patient tissue material to identify niches (in the lung and the brain) that are supportive of metastatic outgrowth and that are relevant in the human setting. The overall goal is to find key vulnerabilities of metastatic TNBC cells that could be targeted in the clinic.

 Candidates must have, or be on track to receive, a First- or Upper Second- class Honours degree (or a Masters) in Biological Sciences and have experience in cancer biology, and must have a basic knowledge of immunology.