ANGIOTENSIN-(1-7) TREATMENT COUNTERACTS METASTASIS INDUCED BY RESISTANCE TO VEGFR INHIBITORS IN BREAST CANCER

CARNEVALE AGUSTINA; SALABERRY PEDRO; SCHOR IGNACIO; KORDON EDITH; WALTHER THOMAS; GATTELLI ALBANA; SCHERE-LEVY, CAROLINA

Mar del Plata

Congreso; Reunión Anual SAIC 2023; 2023

SAIC

Breast cancer metastasis promote by resistance to current therapiesis a crucial factor precluding improvements in mortality. Triplenegative breast cancer (TNBC) is the most aggressive and highlymetastatic tumor subtype with absence of specific therapeutic options.Several inhibitors of tyrosine kinase activity (TKi) have beenevaluated clinically to improve the survival of patients, includingthose that inhibit VEGFR which acts as the master regulator of angiogenesispromoting both tumor growth and metastatic spread.Different anti-VEGFR agents have been developed either TKis asAxitinib (Ax) or antibodies to block the binding of ligand (VEGF) asBevacizumab (Bev). However, its effectiveness is under discussionsince prolonged treatment develops resistance and patient relapsewith metastasis in secondary organs. We studied the role of the renin-angiotensin system (RAS) in breast cancer. We reported that thepro-metastatic action of Angiotensin II (AngII) can be reverted by Angiotensin1-7 [Ang-(1-7)]. Ang-(1-7) is generated by ACE2 enzyme.In renal carcinoma the treatment with Ax generates resistance bydecreasing the expression of ACE2, being able to reverse this effectby adding Ang-(1-7). Herein, we found that treatments with Ax or Bevreduce the expression of ACE2 (p