Title:ACE2/Angiotensin-(1-7)/Mas Receptor Axis in Human Cancer: Potential Role for Pediatric Tumors
Volume: 21
Issue: 9
Author(s): Ana Luiza Ataide Carneiro de Paula Gonzaga , Vitória Andrade Palmeira , Thomas Felipe Silva Ribeiro , Larissa Braga Costa , Karla Emília de Sá Rodrigues and Ana Cristina Simões-e-Silva *
Affiliation:
- Pediatric Branch, Interdisciplinary Laboratory of Medical Investigation, Faculty of Medicine, UFMG,Brazil
Keywords:
Renin-angiotensin system, cancer, pediatric tumor, angiotensin II, angiotensin-(1-7), angiotensin-converting enzyme,
ACE2, angiogenesis.
Abstract:
Background: Pediatric tumors remain the highest cause of death in developed countries.
Research on novel therapeutic strategies with lesser side effects is of utmost importance. In this scenario,
the role of Renin-Angiotensin System (RAS) axes, the classical one formed by angiotensinconverting
enzyme (ACE), Angiotensin II and AT1 receptor and the alternative axis composed by
ACE2, Angiotensin-(1-7) and Mas receptor, have been investigated in cancer.
Objective: This review aimed to summarize the pathophysiological role of RAS in cancer, evidence
for anti-tumor effects of ACE2/Angiotensin-(1-7)/Mas receptor axis and future therapeutic perspectives
for pediatric cancer.
Methods: Pubmed, Scopus and Scielo were searched in regard to RAS molecules in human cancer and
pediatric patients. The search terms were “RAS”, “ACE”, “Angiotensin-(1-7)”, “ACE2”, “Angiotensin
II”, “AT1 receptor”, “Mas receptor”, “Pediatric”, “Cancer”.
Results: Experimental studies have shown that Angiotensin-(1-7) inhibits the growth of tumor cells
and reduces local inflammation and angiogenesis in several types of cancer. Clinical trials with Angiotensin-(
1-7) or TXA127, a pharmaceutical grade formulation of the naturally occurring peptide, have
reported promising findings, but not enough to recommend medical use in human cancer. In regard to
pediatric cancer, only three articles that marginally investigated RAS components were found and
none of them evaluated molecules of the alternative RAS axis.
Conclusion: Despite the potential applicability of Angiotensin-(1-7) in pediatric tumors, the role of
this molecule was never tested. Further clinical trials are necessary, also including pediatric patients,
to confirm safety and efficiency and to define therapeutic targets.
