Renin–Angiotensin System Inhibitors to Mitigate Cancer Treatment–Related Adverse Events

Abstract

Treatment-related side effects are a major clinical problem in cancer treatment. They lead to reduced compliance to therapy as well as increased morbidity and mortality. Well-known are the sequelae of chemotherapy on the heart, especially in childhood cancer survivors. Therefore, measures to mitigate the adverse events of cancer therapy may improve health and quality of life in patients with cancer, both in the short and long term. The renin-angiotensin system (RAS) affects all hallmarks of cancer, and blockage of the RAS is associated with an improved outcome in several cancer types. There is also increasing evidence that inhibition of the RAS might be able to alleviate or even prevent certain types of cancer treatment-related adverse effects. In this review, we summarize the potential of RAS inhibitors to mitigate cancer treatment-related adverse events, with a special emphasis on chemotherapy-induced cardiotoxicity, radiation injury, and arterial hypertension. .

Losartan treatment enhances chemotherapy efficacy and reduces ascites in ovarian cancer models by normalizing the tumor stroma

“…Losartan has been shown to decrease the expression of VEGF (15); however, in our study, we did not observe VEGF expression change after losartan treatment. While we did not investigate it, losartan may also decrease the expression of molecules other than VEGF that are responsible for ascites formation (15,47). Previously, we reported that TGF-β blockade via reducing tumor burden in the diaphragm relieved the compression from the tumor mass on the diaphragm lymphatic vessels and improved their drainage of peritoneal fluid and resulted in reduced ascites in ovarian cancer models (29).…”

Normalizing Function of Tumor Vessels: Progress, Opportunities, and Challenges

“…Retrospective and prospective clinical studies suggest there is a benefit in outcome with ASIs, particularly in slow-growing tumors like prostate and highly aggressive tumors like glioblastoma and pancreatic cancer (46, 70, 119, 120), with the potential to reduce side effects (121). A prospective phase 2 trial in locally advanced pancreatic ductal adenocarcinoma treated with chemoradiation combined with losartan resulted in a remarkably high fraction (61%) of patients having their primary tumor removed without microscopic disease in the margin of the surgical specimen, which suggests increased efficacy and longer survival (122).…”

Small molecule inhibitors of epithelial‐mesenchymal transition for the treatment of cancer and fibrosis

“…Losartan is an AT1R antagonist that improved renal fibrosis by suppressing EMT in rats with hyperglycemia . Although many RAS inhibitors showed beneficial effects in tumors and fibrosis, few were reported to inhibit EMT in the treatment of cancer and fibrosis …”

“…68 Although many RAS inhibitors showed beneficial effects in tumors and fibrosis, few were reported to inhibit EMT in the treatment of cancer and fibrosis. 190,191 2.3 | Targeting miRNA signaling pathways by small molecules MiRNAs are endogenous small noncoding RNAs (19-25 nucleotides) that bind the 3′-untranslated region of messenger RNAs to regulate gene expression. Recently, many miRNAs have been found to promote or suppress EMT in fibrosis and tumors.…”