EVALUATION OF ANGIOTENSIN-(1-7) AS A NEW COMBINATION THERAPY TO REVERSE RESISTANCE TO VEGFR INHIBITORS IN TRIPLE NEGATIVE BREAST CANCER

CARNEVALE AGUSTINA; SALABERRY PEDRO; WALTHER THOMAS; KORDON EDITH; ALBANA GATTELLI; CAROLINA SCHERE LEVY

Mar del Plata

Congreso; Reunión Anual SAIC 2022; 2022

SAIC

In triple negative breast cancer (TNBC) the absence of targetedtreatment and resistance to current therapies are crucial factorsprecluding improvements in mortality. Central in the mechanism ofresistance is the activation of tyrosine kinase receptors, includingVEGFR, the receptor for the main angiogenic factor, VEGF. VEGFRinhibitors as Axitinib (Ax) or Bevacizumab (Bev) succeed in reversingsome cases but in long term, induce resistance and metastaticdisease in other patients. Renin-angiotensin system has been implicatedin multiple aspects of cancer progression through ACE/AngiontensinII (AngII) pathway inducing angiogenesis and metastasis.Angiotensin 1-7 [Ang-(1-7)] is generated from AngII by ACE2enzyme. Previously, we found that AngII promotes invasion of TNBCcell lines by enhancing VEGFR signaling, and Ang-(1-7) counteractspro-tumorigenic actions of AngII. Our group also demonstrated inrenal carcinoma cells that treatment with Ax or Bev decreased ACE2expression, and the addition of Ang-(1-7) in an in vivo combinationtreatment with Ax generated additive suppression of renal tumorgrowth and improved survival outcomes. We determined by bioinformatictools that both ACE and ACE2 are expressed in patientswith TNBC. In this study, our aim is to evaluate in vivo the effectsof combined therapy of Ax + Ang-(1-7) in the treatment of TNBC.As in renal cancer, we found that treatment with Ax or Bev reducesACE2 expression (p