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AACR 2022: Tumor-Specific Second-Generation Imidazolium Compounds Under Study in Bladder Cancer

By: Kayci Reyer
Posted: Friday, April 29, 2022

According to research presented at the American Association for Cancer Research (AACR) Annual Meeting 2022 (Abstract 4058/12), patients with high-risk non–muscle-invasive bladder cancer may benefit from treatment with second-generation imidazolium compounds, which may provide an alternative to intravesical bacillus Calmette-Guérin (BCG) therapy. Previous research has demonstrated the efficacy of first-generation compounds in inducing apoptosis in this patient population.

“[Second-generation] imidazolium compounds are tumor-specific and highly potent compounds that are worthy of further study as an intravesical agent for the treatment of high-grade superficial bladder cancer,” concluded Uttam Satyal, PhD, of the Fox Chase Cancer Center, Philadelphia, and colleagues.

Compared with first-generation compounds, all second-generation imidazolium compounds had superior toxicity to bladder cancer cell lines. In murine models, compounds IS154 and IS155 did not reflect histopathologic change of bladder urothelium in the 24 hours following intravesical administration and were found to be tumor-specific. A total of three potential mitochondrial targets were identified using proteomics data from Stable Isotope Labeling with Amino Acids in Cell Culture (SILAC) testing. The study used CellTiter-Glo and colony-forming assays to analyze the toxicity of second-generation imidazolium compounds versus selected bladder cancer cell lines. Toxicity was evaluated both in vitro using confocal microscopy and in vivo in mouse models.

Disclosure: For full disclosures of the study authors, visit abstractsonline.com.


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