Discovered To Target Her-2/Neu Cancers (February 2000)
Herceptin was approved in 1998 as a new
anticancer drug for the treatment of breast cancers overexpressesing the Her-2/neu gene.
Now researchers at M.D. Anderson Cancer Center, Texas, have discovered another protein
that has the potential to inhibit tumors over-expressing this gene. (Reported in Nature
The Her-2/neu gene is activated when a protein (known as a transcription factor) binds to
its promoter region. Mien-Chie Hung and colleagues discovered that for Her-2/neu, this
activating protein is called PEA3, and comes from a family of proteins called 'Ets'. The
scientists showed that PEA3 administration can prolong the survival of mice bearing human
tumors and that it can block cancer formation in cells in culture.
Thus, PEA3 could be the basis for a new class of anti-cancer drugs that are effective
against tumors over-expressing the Her-2/neu gene, and the findings also validates the
idea that transcription factors from the Ets family could be used to switch off
potentially cancer-causing genes. Good and bad news about gene therapy for brain cancer
Hope for patients with brain cancer, or glioma, has taken a cautious upswing in recent
years with the advent of suicide-gene therapy. The therapy involves injection of an
adenoviral vector (HSV1) carrying the gene for thymidine kinase (TK) into the brain, while
the pro-drug ganciclovir is given systemically. When ganciclovir meets TK in brain cells,
it is activated and destroys not only the cells carrying the gene but also surrounding
cells due to a 'bystander effect.'
Pedro Lowenstein and colleagues at the University of Manchester, UK, have examined the
long-term effects of this relatively new technique. They showed, in a rat model, that the
treatment is very efficient, resulting in tumor destruction and the survival of 80-100% of
animals for at least three months. However, examination of the brains of long-term
survivors, revealed the presence of chronic brain inflammation and nerve cell destruction.
They also found that many more neurons carried HSV1-TK than had been injected with the
These results have implications for ongoing clinical trials of HSV1-TK for glioma. Because
many more cells than anticipated contain HSV1-TK, it may be possible to prolong
ganciclovir administration and improve anti-tumor effects, but this should be weighed
against the negative effects of inflammation and nerve cell destruction.
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