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uppose there were a mutant cold virus that killed only
cancer cells? Or a genetic 'cocktail' whose ingredients could provoke tumor-specific
immune activity? Or what if there were a technique that allowed clinicians
to replace a damaged p53 gene with a normal version? In fact, these are
all therapies under study by head and neck cancer researchers right now.
They are examples of a new approach to cancer treatment known as 'biotherapy.'
Biotherapies are biological, based on the molecules and genes involved in
the cancer process. A decided advantage of these therapies is that unlike
chemically based chemotherapy or physically based radiotherapy -- which
can harm healthy cells as well as tumor cells -- biotherapies can target
tumor cells but leave other cells relatively unscathed. How successful will
these therapies turn out to be? Ongoing research, like that described below,
will eventually be able to give us the answer.
One biotherapy being studied at ONYX Pharmaceuticals has shown success in the clinical setting. The technique consists of a mutant adenovirus that selectively infects and kills only cells that are deficient in p53, such as tumor cells. (Lacking the E1B protein that shuts down p53, the mutant adenovirus can't reproduce in cells with normal p53; but it can replicate in and thus kill cells that do not have functioning p53. See diagram) ONYX has tested this adenovirus in a small number of patients with head and neck cancer who had not responded to surgery, radiation, and in some cases chemotherapy. The adenovirus treatment produced significant destruction of tumors in some patients and lesser improvement in several others. Scientists do not yet know if the tumor cells are dying because of direct viral assault or from attack by the immune system on virus-infected cells.
A different kind of biotherapy uses a type of molecule called a ribozyme,
which is able to bind to and destroy RNA. NIDCR oral cancer researchers at
SUNY in Syracuse have developed ribozymes that destroy the RNA of tumor-associated
human papillomavirus and have devised a method for introducing them into
cancer cells in vitro to inhibit tumor cell growth. Of major importance
was their finding that the tumor suppressor protein, p53, usually absent
in HPV-containing tumor cells, could be detected in the cells into which
ribozymes had been introduced. These results imply that the ribozyme inhibited
the HPV gene product(s) involved in the breakdown of p53. These studies
provide a strong basis for current investigations designed to determine
if ribozymes can inhibit tumor formation in an animal model by the administration
of HPV-positive tumor cells.