Deciphering the melanoma-niche cell interplay to identify novel treatments for m...
Deciphering the melanoma-niche cell interplay to identify novel treatments for metastatic melanoma
Metastasis is the leading cause of death among patients with solid tumours including melanoma, the most serious type of skin cancer. Despite tremendous progress in the development of effective targeted and immunotherapies, patient...
Metastasis is the leading cause of death among patients with solid tumours including melanoma, the most serious type of skin cancer. Despite tremendous progress in the development of effective targeted and immunotherapies, patient survival is still low. Understanding the mechanisms regulating the dissemination of cancer cells is critical to uncover new vulnerabilities of aggressive tumours. Whilst previous research has mostly focused on cell-intrinsic properties of cancer cells, the aim of this project is to define the impact of signals from the cancer cell niche on melanoma dissemination in vivo, with the long-term goal of discovering drug targets and developing new pharmacologic strategies against metastatic melanoma. Building upon previous results from the Ablain laboratory, I will elucidate and target the mechanism by which melanoma cells change their adhesion properties in response to local IGF1 signalling. Additionally, new interactions between melanoma cells and niche cells will be identified by scRNA-seq in human metastatic melanoma tissue obtained from the HCL Hospital, and recapitulated in reconstructed human skin systems and in zebrafish models. I will investigate the role of these interactions in the regulation of melanoma cell behaviour by combining genetic and pharmacologic manipulation with cutting-edge live-imaging in vitro and in vivo. This fellowship, through advanced interdisciplinary and intersectoral training and collaborations, will serve as a launchpad for reaching a position of academic independence, whilst facilitating a transfer of knowledge between myself, the CRCL and several collaborators, and addressing an unmet need for a better understanding of the behaviour of aggressive tumours. I will use this award to expand my skillset, build an international professional network, and establish myself as an expert in the field of cancer cell behaviour, producing high quality, cutting-edge research with strong translational potential.ver más
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