Chemoresistance in triple negative breast cancer: the relation with P2X7 and P2Y2 purinergic receptors

• Grant number: 23/09047-1
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: January 01, 2024
• End date: December 31, 2025
• Field of knowledge: Biological Sciences - Biochemistry
• Principal Investigator: Claudiana Lameu
• Grantee: Fernanda Wagner Caldora
• Host Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Among the different types of existing cancers, breast cancer remains one of the biggest public health problems in the world, since it is the one that most affects women worldwide. In 2022, around 66,280 new cases were estimated in Brazil alone, with 17,825 deaths. The triple negative subtype (TNBC) comprises approximately 15% of breast cancer cases and is the most difficult to treat, since it is the most aggressive breast tumor with the highest rates of recurrence, in addition to high rates of brain metastasis. Treatments for breast cancer diversify according to the types and stages of the tumor, as well as the patient's conditions, and include chemotherapy, radiotherapy, hormone therapy and surgery, with the removal of the tumor or the complete breast. However, many patients with TNBC tend to show resistance to chemotherapy treatment, which worsens their prognosis and increases the rate of metastasis.Recent studies show that chemoresistance and metastasis may be associated with purinergic signaling. Purinergic signaling consists of an extracellular signaling system that promotes immune responses, pain, inflammation, proliferation, cell death, among others, through signaling molecules (nucleosides and nucleotides) that bind to purinergic receptors, which perform their functions in the body. It has been shown that purinergic signaling regulates the proliferation, differentiation and cell death of stem cells of different origins. Among the purinergic receptors, P2X7 is the most expressed in tumor cell lines and in human primary tumors, being hardly found in healthy breast tissues, but with greater expression in breast cancer tissues. As for the P2Y2 receptor, it was verified that its activation increases the invasive capacity of breast cancer cells, through the induction of the epithelial-mesenchymal transition (EMT).Therefore, it becomes necessary to understand the functioning of chemoresistance in triple negative breast cancer, as well as its relationship with purinergic signaling. Thus, it is also possible to contribute to a future identification of effective therapeutic targets against the disease.