Our ACE in the HOLE: Justifying the Use of Angiotensin-converting Enzyme Inhibitors as Adjuvants to Standard Chemotherapy

Schematic pathway diagram of the oncogenic actions of angiontensinconverting enzyme (ACE) in cancer and inhibition by ACE inhibitors approved by the federal drug administration. Angiotensin I (AGI) conversion to angiotensin II (AGII) and binding to its conjugate receptor (AGII-R) initiates an extracellular signal-related-1/2 (ERK1/2) and phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling cascade which results in up regulation of vascular endothelial growth factor-alpha (VEGFA). Inhibition of angiotensin II production results in decreased VEGF production and mitigated microvascular production, which corresponds to lowered nutrient uptake and stunted tumor growth in vivo.