Breast cancer is the second leading cause of cancer death in women and 2.1 million new patients are diagnosed each year with this disease, reported by the World Health Organization (WHO) in 2020. My EPICAN research project aimed at understanding the origin of intra tumor heterogeneity in breast cancer. Despite its clonal origin, cancer is heterogeneous by nature, due to the intrinsic genetic and epigenetic alterations and the multi clonal evolution of the disease, and due to the crosstalk between the cancer cells and their micro-environment. Such tumor heterogeneity is an important source of fitness for cancer, and constitute a major hurdle to develop efficient anti-cancer therapies. In this project, I aim at understanding how oncogenic activation of the PI3K pathway (e.g. PIK3CAH1047R…), hyperactive in more than 70% of breast cancers, increases tumor cell plasticity to generate tumor heterogeneity.
Breast cancer is the leading cause of cancer death among females, with 685,000 deaths annually. Breast cancer has dramatic effects on quality of life and socio-economics factors, and is clearly a major society issue worldwide, regardless of the index of development. This research project, despite its fundamental rationale, is of major interest for breast cancer patients. Indeed, there is a crucial need to identify new predictive biomarkers and novel therapeutic targets, to improve patient stratification and to develop efficient anti-cancer therapies to block disease progression. Genetic mutations conferring oncogenic activation of the PI3K pathway are among the most frequent in breast cancer together with TP53 deletions. Besides, the first targeted therapy (Alpelisib) for patients bearing PIK3CA mutations has recently been approved, thus raising great hopes for better care of breast cancer patients (SOLAR-1 Trial). However, as mechanisms of resistance frequently emerge following targeted therapy administration, cancer cells may escape the therapeutic pressure imposed by Alpelisib. It is therefore of paramount clinical interest to anticipate such phenomenon and to investigate the molecular mechanisms promoting tumor cell heterogeneity, in order to enhance the efficacy of such targeted therapies and prevent relapses. This is the goal the of my research project.
