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Thomas Flaig, MD


Novel Targeted Aptamer-Drug Conjugate Under Study in Bladder Cancer

By: Sarah Lynch
Posted: Friday, March 3, 2023

Researchers recently discovered the potential of a a targeted aptamer-drug conjugate in treating bladder cancer: protein tyrosine kinase 7 (PTK7) aptamer plus gemcitabine. This biomarker-oriented, tumor-targeted therapy demonstrated antitumor efficacy and general biosafety. Liu et al, of the Third Xiangya Hospital of Central South University, Changsha, China, reported these research findings in Biomaterials Research.

“Although advances in surgical treatments and combination chemotherapy (cisplatin and gemcitabine) protocols have improved median survival, approximately 50% of patients with [bladder cancer] develop recurrent or metastatic disease…,” the investigators stated. “Chemoresistance and side effects of classical anticancer drugs occur during treatment, immune checkpoint inhibitors induce their off-target effects, antibody-drug conjugates immunogenicity risk, and the increased incidence of drug resistance remain challenges.”

PTK7 was determined to be commonly overexpressed in bladder cancer cells through analysis of certain databases. The investigators then evaluated the antitumor effects and safety of the PTK7-gemcitabine conjugate both in vitro and in vivo. They found the combination may bind and enter bladder cancer cells based on the cells’ expression of PTK7 and through the macropinocytosis pathway, which then induced cytotoxicity after gemcitabine cleavage from the PTK7-gemcitabine conjugate response to phosphatase in the cell.

According to the investigators, the novel targeting system improved the efficacy of gemcitabine in the treatment of bladder cancer by increasing its ability to recognize tumor cells, leading to high systemic toxicity and chemotherapy resistance. The results of this research indicated the PTK7 aptamer plus gemcitabine was successful in targeting bladder cancer cells and may provide a new direction for the development of new treatments of bladder cancer within the field of biomarker-oriented tumor therapy.

Disclosure: The study authors reported no conflicts of interest.

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