Breast cancer is the most common cancer in women and, after lung cancer, the second leading cause of cancer-related deaths. The most important factor influencing the outcome of patients with an invasive cancer is whether the tumour has spread regionally or systemically. Breast cancer dissemination is a multi-step process, affected by intrinsic, as well as by microenvironmental factors. Metastases start out as single cells that detach from the primary tumour and travel to distal locations. The number of circulating tumour cells before treatment is an independent predictor of progression-free survival and overall survival in patients with metastatic breast cancer. The biology of these cells is not well comprehended and its understanding is critical for therapeutic improvements. One of the key questions that remain to be fully resolved is what molecular events allow the survival of cancer cells in hostile environment of peripheral blood. Recently, a novel concept arose redefining the molecular basis of survival of breast cancer cells. According to this concept, tumour cells can utilize intracellular (intracrine) receptor-ligand interactions to produce signals necessary for tumour survival under unfavourable conditions. A major scientific objective of the proposed project is to generate, using a transgenic approach, the animal model systems of breast cancer allowing to study the role of intracrine signalling in survival of disseminating breast cancer cells. The work activities detailed in this proposal will have a significant impact on the understanding of the mechanisms of metastasis in early stage breast cancer and thus will facilitate the prevention and/or fight against metastatic breast cancer.
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