Protein Kinases and Cancer

Our laboratory’s perspective is to advance the understanding of the mechanisms mediated by the PI3K/AKT/mTOR/S6 and cyclin D1/CDK4/6/Rb pathways in the progression of breast cancer. Ultimately, we aim to define new markers associated with disease evolution. The significance of our research lies in the activation of these signaling pathways is proposed as a major tumor escape mechanism, particularly during resistance to conventional systemic therapies.

New specific inhibitors, such as PI3K, mTOR, and CDK4/6 inhibitors, have been incorporated into clinical practice in the past five years. However, there is no consensus on which molecular markers of pathway activation are most strongly associated with patient outcomes, nor is it clear how the activation of these pathways’ changes following exposure to targeted therapies. Therefore, we aim to deepen our understanding of the roles of the PI3K/AKT/mTOR/S6 and cyclin D1/CDK4/6/Rb pathways in disease progression and breast cancer response to currently available therapeutic agents.

To achieve this, we analyze tumors from breast cancer patients to identify molecular markers and utilize experimental models, including mouse-induced breast tumors and xenografts of tumor cell lines. These models allow us to test the most effective therapeutic options based on the markers identified.

The lines of research we are developing include:

1) Prognostic Factors: Utilizing AKT1 and AKT2 isoforms as prognostic indicators in breast cancer.

2) Pathway Interaction: Investigating the interaction between the PI3K/AKT/mTOR/S6 and CDK4-6/Rb/cyclin D1 pathways as predictive factors for responses to anti-tumor treatments.

3) MicroRNA Profiling: Identifying specific microRNAs involved in the differential regulation of protein kinases to establish peripheral markers for diagnosis and monitoring.