The Chromoscience

SRT1720 Experimental Drug Inhibits Bladder Cancer Development

Benison P. Zerrudo
1–2 minutes

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https://www.std-gov.org/blog/bladder-function/

  • 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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Sources:

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

[1] https://en.wikipedia.org/wiki/SRT-1720

[2] https://pubmed.ncbi.nlm.nih.gov/29094888

[3] https://www.cancer.gov/types/bladder

[4] https://en.wikipedia.org/wiki/Organoid

[5] https://pubmed.ncbi.nlm.nih.gov/24020000

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The Chromoscience uses AI-assisted tools to support the preparation and editing of science articles. Content is reviewed by the editor for clarity and consistency with the cited research before publication. Readers are encouraged to consult the original scientific publications for complete findings, methods, and limitations.

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