Research Highlights: SRT1720 Experimental Drug Inhibits Bladder Cancer Development

SRT1720 Experimental Drug Inhibits Bladder Cancer Development

  • Bladder cancer is the sixth most common malignancy in the United States.[2]
  • The most common clinical presentation of bladder cancer is the presence of blood in the urine.[2]
  • Smoking is a major risk factor for bladder cancer.[3]
  • 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.[4]
  • 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.[1]
  • SIRT1 is a gene involved in the deacetylation of histones and a number of nonhistone substrates that can affect multiple signaling pathways.[5]
  • Many studies showed that SIRT1 could act as either a tumor suppressor or tumor promoter depending on its targets in specific cancers.[5]
  • 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.

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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).