Protocolo de cribado de complicaciones inguinales mediante ultrasonografía en pacientes con ictus sometidos a procedimiento endovascular / IL1RAP targeting as a new therapeutic strategy for advanced triple negative breast cancer: Identification of response biomarkers and mechanisms of action

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The interleukin-1 (IL-1) family of cytokines is key for the inflammatory microenvironment of many tumors, including breast cancer (BC). It is involved in tumor growth, metastasis and development of chemo resistance. To activate the IL-1 pathway, the IL-1 receptor 1 (IL1R1) must dimerize with IL-1 receptor accessory protein (IL1RAP). IL1RAP is highly expressed in several cancers, including BC, as compared to normal tissue. Triple negative breast cancer (TNBC) is more likely to metastasise, leading to a more aggressive form. Unfortunately, there is still a lack of effective targeted therapies for TNBC patients. Nadunolimab (CAN04) is an ADCC-enhanced monoclonal IgG1antibody targeting IL1RAP that blocks IL-1α and IL-1β signaling and is currently being investigated in combination with gemcitabine and carboplatin as a new therapeutic strategy for TNBC patients in the TRIFOUR clinical trial (NCT05181462), in which we participate. Our hypothesis is that IL1RAP plays an important role in TNBC progression and metastasis. In this project we investigate nadunolimab mechanism of action and decipher predictive biomarkers by analysing serum and tumor samples from the TRIFOUR trial, as well as investigate its effect in cell culture and preclinical in vivo models.