P53 modulator and cancer target

Abstract

Methods of screening for modulators of TRIM24 (also known as TIF1-ALPHA) expression and / or biological activity are described. In particular, methods of screening for modulators of TRIM24 E3 ligase activity, and specifically an E3 ligase activity directed at p53 as the target polypeptide are also described. Modulators of TRIM24 expression and activity are provided and their use in treatment of cancer, particularly in breast, colon, prostate, renal cancers and in acute lymphoblastic leukemia. Suitable modulators of TRIM24 expression include siRNA and shRNA and can be used in the treatment of cancer and for targeting cancer stem cells.

Description

FIELD OF THE INVENTION[0001]The invention relates to the detection and treatment of cancers. In particular, the invention relates to the identification of a novel binding partner of p53, which shows modified expression patterns in certain cancer types; to methods for identifying modulators of the interaction between p53 and the novel binding partner; and the use of such modulators for the treatment of cancer.BACKGROUND OF THE INVENTION[0002]Cancer is the second leading cause of death in the United States. An estimated 10.1 million Americans are living with a previous diagnosis of cancer. In 2002, over one million people were newly diagnosed with cancer in the United States (information from Centres for Disease Control and Prevention, 2004 and 2005, and National Cancer Institute, 2005). According to Cancer Research UK, in 2005 over 150,000 people died in the UK as a result of cancer. It has been reported that almost 44,100 cases of breast cancer are diagnosed in the UK each year (i.e...

AI Technical Summary

Benefits of technology

The method enables the detection of cancer at an early stage and provides a treatment approach by modulating p53 activity through TRIM24 regulation, potentially improving cancer diagnosis and treatment outcomes.

Problems solved by technology

Hence, where the expression of a tumour suppressor gene has been inhibited, DNA mutations are able to accumulate unchecked and, almost inevitably, will lead to cancer.

However, many cancers cannot be detected by such crude examinations and, in these cases, other forms of physical and / or biochemical examinations may be required.

There remains, however, a large number of different types of human cancer, which are not readily detectable, or reliably detectable, by present screening methods, prior to the onset of disease symptoms (by which time it may be too late for an effective intervention).

Images