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Method of Detecting and Targeting Mutations in Cancer

Byard Edwards¹

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1. Stanford University, Department of Radiology

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Document Type:

Manuscript

Date:

Received 13 November 2007 22:02 UTC; Posted 13 November 2007

Subjects:

Cancer

Tags:

• DNA-binding protein
• tumor
• therapeutic
• zinc-finger

Abstract:

While there are many differences between tumor and non-tumor cells, the basic underlying distinction is in the DNA. Tumor cells harbor mutations, at least some of which are not present in non-tumor cells. Thus, a method of directly targeting cells containing specific mutations has potential for detection or treatment of cancer without the toxicity associated with more indirect approaches. Also, as mutations are a necessary component of malignancy, such a method is potentially applicable to all tumors.

I propose a method by which several recently developed techniques can be utilized in a novel way to accomplish the goal of directly targeting mutations for cancer detection and therapy. The model can be summarized as follows: (1) Determine potential target mutations present in tumor cells but not non-tumor cells. (2) Construct molecules that will bind to DNA at the sites of mutation, but will not bind to DNA in normal cells. And, as a consequence of the molecules binding to the mutation, the cells will be destroyed. (3) Deliver these molecules to all cells (or at least all tumor cells). I hypothesize that such molecules can now be constructed using sequence-specific DNA binding proteins (such as customized zinc-finger DNA binding proteins) fused to transcriptional activator domains (such as VP16) and reporter or toxin genes. The necessary genes can be linked to the DNA binding proteins utilizing a recently described method based on expressed protein ligation.

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This document is licensed to the public under the Creative Commons Attribution 3.0 License

How to cite this document:

Edwards, Byard. Method of Detecting and Targeting Mutations in Cancer. Available from Nature Precedings <http://dx.doi.org/10.1038/npre.2007.1314.1> (2007)

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