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Project

Preclinical evaluation of saRNA-guided p21 activation for bladder cancer

Funder: American Association For Cancer Research

Funding period
USD 252 K
Funding amount
Abstract
Bladder cancer is the fourth most common cancer in men in the United States, after prostate, lung, and colorectal cancer and the tenth most common cancer in women. The American Cancer Society estimates that 68,810 new cases of bladder cancer will be found in the United States during 2008 and about 14,100 people will die of this disease. Early stage bladder cancer can be treated by a procedure called transurethral resection or TUR. However, cancer will recur in over 60% of TRU treated patients with some coming back in a more aggressive form and at an advanced stage. There is no effective treatment for advanced bladder cancer without completely removing the bladder. A hallmark of cancer cells is their uncontrolled proliferation and reduced death resulting from an imbalance of overactive tumor promoting genes and the loss or silencing of tumor suppressor genes. The p21 gene is one of such critical tumor suppressor genes that inhibit cell proliferation and its expression is turned off in most bladder cancer. Recently we have found a new way of switching on tumor suppressor genes using small RNA as a gene expression booster and have demonstrated that turning on p21 gene using small RNA dramatically inhibits the growth of cultured bladder cancer cells. In the present study, we will first optimize our previous experiments through designing more effective small RNAs to achieve a maximal inhibition of cultured bladder cancer cells, and will then treat human bladder cancer that has been implanted in mouse bladder with p21 gene targeted small RNAs delivered to the bladder via the urethra. This pre-clinical animal study will provide valuable data on the in vivo efficacy and toxicity of small RNAs and the data will be critical for us to pursue our ultimate goal of treating bladder cancer patients with the small RNA drugs validated in the animal study.
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System

Categories
  • FOR (ANZSRC)

    1112 Oncology and Carcinogenesis

  • RCDC

    Biotechnology

  • RCDC

    Lung

  • RCDC

    Cancer

  • RCDC

    Clinical Research

  • RCDC

    Genetics

  • RCDC

    Urologic Diseases

  • HRCS HC

    Cancer

  • HRCS RAC

    5.1 Pharmaceuticals

  • Health Research Areas

    Biomedical

  • Broad Research Areas

    Basic Science