Losartan improves the therapeutic effect of metronomic cyclophosphamide in triple negative mammary cancer models.

Losartan improves the therapeutic effect of metronomic cyclophosphamide in triple negative mammary cancer models. Oncotarget. 2020 Aug 11;11(32):3048-3060 Authors: Mainetti LE, Rico MJ, Kaufman CD, Grillo MC, Guercetti J, Baglioni MV, Del Giúdice A, Capitani MC, Fusini M, Rozados VR, Scharovsky OG Abstract Metronomic chemotherapy refers to the minimum biologically effective doses of a chemotherapy agent given as a continuous regimen without extended rest periods. Drug repurposing is defined as the use of an already known drug for a new medical indication, different from the original one. In oncology the combination of these two therapeutic approaches is called "Metronomics". The aim of this work is to evaluate the therapeutic effect of cyclophosphamide in a metronomic schedule in combination with the repurposed drug losartan in two genetically different mice models of triple negative breast cancer. Our findings showed that adding losartan to metronomic cyclophosphamide significantly improved the therapeutic outcome. In both models the combined treatment increased the mice's survival without sings of toxicity. Moreover, we elucidated some of the mechanisms of action involved, which include a decrease of intratumor hypoxia, stimulation of the immune response and remodeling of the tumor microenvironment. The remarkable therapeutic effect, the lack of toxicity, the low cost of the drugs and its oral administration, strongly suggest its ...
Source: Oncotarget - Category: Cancer & Oncology Tags: Oncotarget Source Type: research