Key result
ACE inhibitors failed to reduce or delay proteinuria caused by anti-angiogenic drugs and compromised their anticancer efficacy by promoting the production of kidney-derived erythropoietin.
Why the study?
Anti-angiogenic drugs used for hepatocellular carcinoma cause proteinuria, but whether ACEIs effectively alleviate this proteinuria or promote cancer progression remains controversial.
Does the addition of ACEIs to AADs reduce proteinuria and maintain anti-cancer efficacy in hepatocellular carcinoma?
Does the addition of ACEIs to AADs reduce proteinuria and maintain anti-cancer efficacy in hepatocellular carcinoma?
The use of ACEIs to treat AAD-induced proteinuria in HCC is ineffective and may compromise the anti-tumor efficacy of AADs by increasing renal EPO production.
Answers are grounded in this paper and cite their sources.
ACE inhibitors should not be used for anti-angiogenic drug-induced proteinuria; hypothesis-generating that they may impair anticancer efficacy.
Anti-angiogenic drugs (AADs) are currently the main choice for systemic treatment of hepatocellular carcinoma, but treatment-related proteinuria can affect the routine use of AADs, which in turn affects the overall efficacy, its prevention is a clinical aspiration. At present, most clinicians give angiotensin-converting enzyme inhibitors (ACEIs) to alleviate proteinuria according to diabetic nephropathy guidelines or expert recommendations. However, its efficacy and whether it promotes cancer are controversial. Our clinical work has found that the use of ACEIs has not effectively relieved proteinuria, and some cases even have obvious tumor progression. Here we confirmed that in different tumor-bearing mouse models, ACEIs not only did not delay the appearance of proteinuria or reduce the degree of proteinuria caused by AADs, but also reduced the anti-cancer efficacy of AADs, and the reduction of anticancer efficacy has nothing to do with the change of VEGF signaling pathway, Our study show the combination of ACEIs and AADs aggravates the production of kidney-derived erythropoietin(EPO). In turn, EPO compromises the anti-angiogenic effects of AADs and decreases antitumor activity. This study presents treatment of proteinuria caused by AADs with ACEIs is useless and plays a role in drug resistance. Our purpose is to contribute to the rational management of side effects of AADs and to develop relevant guidelines.
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Zhang et al. (2020) studied Hepatocellular carcinoma with anti-angiogenic drug-induced proteinuria. ACE inhibitors (captopril, enalapril, fosinopril) vs. Anti-angiogenic drugs alone (apatinib or regorafenib) was evaluated. ACE inhibitors failed to reduce or delay proteinuria caused by anti-angiogenic drugs and compromised their anticancer efficacy by promoting the production of kidney-derived erythropoietin.
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