Protein Kinases and Molecular Oncology

Resistance to conventional treatments in breast cancer is highly frequent, affecting approximately 14,000 patients per year in our country. In our laboratory, we study how the dysregulation of certain proteins and microRNAs occurs in the evolution of breast cancer in order to identify new biomarkers that will allow for better patient stratification, improve treatment outcomes, and predict which patients will relapse after a particular treatment to provide the best therapeutic option to each patient.
Clinical approaches in cancer where the therapeutic strategy is determined based on the expression of a particular targeted pathway are scarce. Such is the case of the presence of alterations in the PI3K catalytic subunit alpha gene (PIK3CA), called PIK3CAmutant, in both tumor tissue and free circular DNA to indicate the use of alpelisib, a specific PI3Kα inhibitor, in advanced breast cancer. However, besides the high costs associated with determining PIK3CAmutant, it should be considered that determining alterations in a single gene may not be entirely informative. For this reason, using preclinical experimental models and samples from breast cancer patients, in collaboration with oncologists from the Alexander Fleming Institute, Pirovano Hospital, and the Provincial Hospital of Neuquén, we are working on the search for new tumor biomarkers that facilitate the clinical follow-up of breast cancer and that could eventually be used for diagnostic, prognostic, and predictive purposes regarding therapeutic response. We propose implementing other more accessible detection methods and expanding the determination to other factors of the PI3K pathway, while also adding components of other related pathways, such as CDK4/6, involved in resistance and tumor escape mechanisms. In this way, we hope to contribute to broadening and facilitating the availability of biomarkers that can be used in the clinic to better stratify breast tumors and direct therapeutic strategies in a more specific and selective manner.

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