Angiotensin-(1-7) treatment counteracts metastasis induced by resistance to VEGFR inhibitors in breast cancer.

CARNEVALE, AGUSTINA; SALABERRY, PEDRO; LARA, ANGELA; PALAVECINO, MARCOS; SCHOR, IGNACIO; WALTHER, THOMAS; KORDON, EDITH; GATTELLI, ALBANA; SCHERE LEVY, CAROLINA

Congreso; Reunión anual de la Sociedad Argentina de Investigación Clínica (SAIC); 2023

Breast cancer metastasis promote by resistance to current therapies is a crucial factor precluding improvements in mortality. Triple negative breast cancer (TNBC) is the most aggressive and highly metastatic tumor subtype with absence of specific therapeutic options. Several inhibitors of tyrosine kinase activity (TKi) have been evaluated clinically to improve the survival of patients, including those that inhibit VEGFR which acts as the master regulator of angiogenesis promoting both tumor growth and metastatic spread. Different anti-VEGFR agents have been developed either TKis as Axitinib (Ax) or antibodies to block the binding of ligand (VEGF) as Bevacizumab (Bev). However, its effectiveness is under discussion since prolonged treatment develops resistance and patient relapse with metastasis in secondary organs. We studied the role of the renin-angiotensin system (RAS) in breast cancer. We reported that the pro-metastatic action of Angiotensin II (AngII) can be reverted by Angiotensin 1-7 [Ang-(1-7)]. Ang-(1-7) is generated by ACE2 enzyme. In renal carcinoma the treatment with Ax generates resistance by decreasing the expression of ACE2, being able to reverse this effect by adding Ang-(1-7). Herein, we found that treatments with Ax or Bev reduce the expression of ACE2 (p