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Targeting microRNAs for ColoRectal Cancer Therapy

Final Report Summary - TAMIRCRT (Targeting microRNAs for ColoRectal Cancer Therapy)

The work carried out during my Career Integration Grant involved the analysis of microRNA deregulation in colorectal cancer and the discovery of novel methods to target microRNA deregulation. We screened and analysed microRNA expression in primary and metastatic colorectal cancer cases collected as part of clinical trials as well as publically available databases. We published data highlighting the contribution of some of these microRNAs in colorectal cancer initiation and progression and their potential predictive and prognostic role. More recently we ran high-throughput siRNA and drug screenings to define vulnerabilities and mechanisms of resistance associated with microRNA deregulation. We validated hits from our screenings in vitro and in vivo by using colorectal cancer patients’ material. We also identified microRNAs promoting cancer phenotype downstream of oncogenic pathways such as KRAS, TP53 and PTEN. We studied the contribution of these microRNAs in controlling cell adhesion, metabolism and angiogenesis. The definition of molecular mechanisms of drug sensitivity or resistance associated with microRNA deregulation may help to tailor cancer treatment by defining novel therapeutic strategies and implementing patient’s stratification in prospective studies.
The Career Integration Grant contributed toward the set-up of my own research group and allowed me to generate preliminary data that proved to be critical in getting further internal (Institute of Cancer Research London) and external research funding from cancer charities (Cancer Research UK) and the National Health System through the National Institute for Health Research in England.
The Career Integration Grant also contributed to transfer my knowledge and my skills in the area of microRNAs to other fields of application and other institutions in Europe as supported by a number of novel collaborations with Institutions in Italy and Sweden. These collaborations involve the use of microRNAs as predictive/prognostic biomarkers in cancer and internal medicine.
The award of the Career Integration Grant represented a crucial step in my re-integration in Europe as it provided me with research funding when I needed it most and also because it represented an important credential to secure additional financial support and a long term position in one of the top ranking research institutions in Europe facilitating my transition to a permanent position as a clinician/scientist.