Bladder cancer is the most common malignant disease of the urinary system and occurs more frequently in men with a history of smoking. Worldwide, more than 430,000 new patients are diagnosed with bladder cancer annually, and 180,000 individuals die from it. Although more than 75% of bladder cancers are detected at an early stage, there are types that already have genetic abnormalities and are prone to malignant progression even at early stages, leading to recurrence, systemic metastasis, and death.
The research group led by Designated Assistant Professor Kazuki Heishima and Specially-Appointed Professor Yukihiro Akao of the United Graduate School of Drug Discovery and Medical Information Sciences at Gifu University found that early lesions that develop in rats given the smoking-related chemical BBN (N-Butyl-N-(4-Hydroxybutyl)nitrosamine), under certain conditions, are very similar in nature to early-stage bladder cancer in humans, which tends to progress to malignant forms.
Studies on the animal model have revealed that the level of microRNA-145 (miR-145) decreases from the very early stages of lesion formation, and that early bladder cancer is induced through the regulation of many oncogenes. Therefore, decreased miR-145 was found to play a central role in the development and progression of this cancer type. Furthermore, the researchers have improved the chemical structure of miR-145 and developed miR145-S1, a new nucleic acid drug seed with high anticancer activity. The intravesical administration of the nucleic acid drug candidate into the bladder of a mouse model at an early-stage bladder cancer, followed by the supplementation of miR-145 expression, demonstrated that the suppression in the malignant progression of early-stage lesions.
In the future, this novel nucleic acid drug candidate is expected to be developed as a drug for suppressing the malignant progression of early-stage bladder cancer. Additionally, the application of the animal model established by this research group will accelerate research into treatments for early-stage bladder cancer.
Publication: Molecular Therapy Nucleic Acids
Title: Targeting microRNA-145-mediated progressive phenotypes of early bladder cancer in a molecularly defined in vivo model
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