The role of angiogenin in bladder cancer: where are we in 2025?

Abstract

Purpose: The diagnosis of bladder cancer (BCa), a condition that represents approximately 4% of new cancer cases in the United States, could be greatly improved by the development of non-invasive biomarker-based testing. Current diagnostic methods include cystoscopy and cytology; however, these techniques are overly invasive and may cause patient discomfort. Angiogenin (ANG), a member of the RNase A superfamily, was implicated in tumor growth due to its role in angiogenesis. ANG pathophysiology and potential diagnostic and therapeutic role in BCa are discussed.

Methods: A narrative review was conducted on the relationship between ANG and BCa. Articles were retrieved from PubMed and Google Scholar between the years of 2000 and 2024. The authors reviewed the included articles and summarized findings.

Results: In BCa, ANG interacts with matrix metallopeptidase 2 (MMP2) through the ERK1/2 signaling pathway and contributes to extracellular matrix (ECM) degradation. This review, including 9 articles that directly assessed biomarker-based tests with ANG, suggests that ANG may be suitable for developing novel diagnostic urine biomarker tests. The overexpression of ANG in patients with BCa may also suggest the potential for developing therapeutics that target this protein. Some articles indicate that ribonuclease inhibitors could successfully target ANG by limiting nuclear translocation or limiting ANG activation of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathways, thus limiting BCa progression.

Conclusions: The results of this review warrant further investigation into both the diagnostic and therapeutic potential of ANG in BCa. Future case-control studies and clinical trials are needed.

Keywords: Angiogenin; Biomarker tests; Bladder cancer; Non-invasive diagnostics.