Protein Kinases and Cancer

The perspective of our laboratory is to advance our understanding of the mechanisms mediated by the PI3K/AKT/mTOR and cyclin D1/CDK4/6/Rb pathways in the progression of luminal-type breast cancer and eventually define new markers associated with disease evolution. The impact of our research lies in the fact that the activation of these signaling pathways is proposed as tumor escape mechanisms, fundamentally during resistance to conventional systemic therapies. In the last 5 years, new specific inhibitors against these pathways, PI3K, mTOR and CDK4/6 inhibitors, have been incorporated into clinical practice. However, there is still no consensus on which are the molecular markers of activation of each pathway that are best associated with the clinical evolution of patients. It is also not known how the activation of these pathways is modified after exposing patients to targeted therapies. For this reason, we want to deepen our knowledge of the role of PI3K/AKT/mTOR and cyclin D1/CDK4/6/Rb in the mechanisms involved in the progression of the disease and in the response of breast cancer to available therapeutic agents. To do this, we test tumors from patients with the disease to find molecular markers, and we use experimental models of breast tumors induced in mice, as well as xenografts of tumor cell lines, to test the most beneficial therapeutic options according to the markers found.

The lines of work that we develop are:

1) Use of AKT1 and AKT2 isoforms as prognostic factors in breast cancer
2) Study of the interaction between the PI3K/AKT/mTOR and CDK4-6/Rb/cyclin D1 pathways as a predictor of tumor response
3) Determination of specific microRNAs involved in the differential regulation of protein kinases to provide peripheral diagnostic markers.