SRT1720 Experimental Drug Inhibits Bladder Cancer Development
- Bladder cancer is the sixth most common malignancy in the United States.
- The most common clinical presentation of bladder cancer is the presence of blood in the urine.
- Smoking is a major risk factor for bladder cancer.
- New therapeutic targets and drugs for bladder cancer are needed in clinical settings.
- Most of the past research relied on limited bladder cancer cell lines.
- Tumor heterogeneity and pathology of this disease are not well represented with limited bladder cancer cell lines.
- An organoid is a small and simplified version of an organ produced in three dimensions that shows realistic micro-anatomy.
- Cancer organoids can repeat pathological and molecular properties of bladder cancer.
- Researchers evaluate the first bladder cancer organoid-based molecule, SRT1720, for epigenetic drugs.
- SRT1720 is a drug that was studied by Sirtris Pharmaceuticals intended as a small-molecule activator of the sirtuin subtype SIRT1.
- SIRT1 is a gene involved in the deacetylation of histones and a number of nonhistone substrates that can affect multiple signaling pathways.
- Many studies showed that SIRT1 could act as either a tumor suppressor or tumor promoter depending on its targets in specific cancers.
- Researchers found that SRT1720 significantly inhibits the development of both mouse and human bladder cancer organoids.
- SRT1720 also prevents the development of bladder cancer in mouse and human patient-derived xenograft bladder cancer.
- When SIRT1 is mutated, the growth of cancer organoids is increased and their sensitivity to SRT1720 is decreased.
- The finding proves that SRT1720 targets the SIRT1 in bladder cancer.
- Researchers also found that SRT1720 treatment can inhibit the development of hypoxia.
- Additionally, the SIRT1-repressed gene signature is linked with the hypoxia target gene signature and poor prognosis in human bladder cancer.
- The study demonstrated the power of drug discovery using cancer organoids and identifies SRT1720 as a new therapy for bladder cancer.
Tan, P., Wang, M., Zhong, A. et al. SRT1720 inhibits the growth of bladder cancer in organoids and murine models through the SIRT1-HIF axis. Oncogene (2021). https://doi.org/10.1038/s41388-021-01999-9