Onkológia 5/2020

Relevance of the PI3K signaling pathway in advanced breast cancer and the possibilities of targeted treatment

Hormone positive carcinomas represent the dominant group of breast tumors. Hormone therapy is highly effective, with a favorable toxicity profile compared to chemotherapy. However, a key issue in the treatment of advanced disease is the acquired resistance to hormonal treatment. Approximately 40% of patients carry mutations in the PIK3CA gene that cause activation of the phosphatidylinositol 3-kinase (PI3K) signaling cascade responsible for proliferation, migration, and survival of tumor cells. Activation of the PI3K cascade and its interaction with the estrogen receptor signaling pathway is responsible for the development of hormonal resistance. Effectively influencing the PIK3 signaling pathway appears to be a way to overcome hormonal resistance with an effect on the therapeutic outcome, especially in patients with activating PIK3CA mutations. Targeted biologic therapy based on the identification of mutations in the tumor genome represents a significant advance in the further personalization of breast cancer treatment.

Keywords: breast cancer, PI3K signaling pathway, PIK3CA, alpelisib