• Thu, May 29 2008

Nanotechnology and gene p53

P52 gene, arrows show locations of common mutations 

(Image courtesy www.bioinf.org)

Following on from my last article on using gene therapy for increasing survival in head and neck cancer, Professor Jack Roth, M.D., professor in M. D. Anderson’s Department of Thoracic & Cardiovascular Surgery and colleagues are now focusing on ways to deliver p53 and other tumor-suppressing genes systemically – through intravenous delivery.

The p53 gene is inactivated in many types of cancer. Its normal role is to halt the division of a defective cell and then force the cell to kill itself.

Advexin has to be injected straight into the tumor, but that’s not workable for many cancers. Head and neck cancer kills patients by recurring, not spreading to other organs, but most cancer deaths involve metastasis.

By wrapping tumor-suppressing genes in tiny balls of fat, Roth and colleagues hope to be able to treat more invasive cancers. While p53 nanoparticles are still in preclinical development, those that deliver another tumor-suppressor called FUS1 are in a phase I clinical trial for non-small cell lung cancer. Through 19 patients, the dose escalation study has yet to encounter significant side effects.

Injected nanoparticles gather mainly in tumors, where they are taken up and dissolved, leaving the tumor-suppressor gene at work in the cell. A version that combines FUS1 and p53 is under development.

Elaine Warburton  www.geneticsandhealth.com

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