Researchers announced recently that they have developed a new system
to deliver the p53 tumor suppressor gene directly into the tumor
through the bloodstream. The system, when used in combination with
radiotherapy and chemotherapy, may significantly improve treatment
outcomes for prostate cancer patients. The findings were presented at
the International Conference on Molecular Cancer Therapeutics
sponsored by the American Association of Cancer Research (AACR),
National Cancer Institute (NCI), and European Organization for
Research and Treatment of Cancer (EORTC).
Our data demonstrate that by introducing p53 in this new way,
we can sensitize prostate tumors to radiation and chemotherapeutic
agents. Also, by delivering the p53 gene directly into the
bloodstream, we can increase the number of cancer cells that are
targeted and reachedthe cells of the actual tumor and those
that may be roaming throughout the body, said Kathleen F.
Pirollo, PhD, research associate professor at the Lombardi Cancer
Center at Georgetown University in Washington, DC.
Abnormalities in p53 have been found in the majority of human
cancers. This gene is influential in causing apoptosis, and has been
the focus of several studies attempting to introduce
normal copies of the gene into cancer cells in order to
stop the disease. The most common way of introducing the normal p53
gene into cancer cells is to use an adenovirus as a carrier. However,
limitations to this method include the number of cells reached, the
ability to target only the cancer cells, and possible adverse effects.
Three Compounds Comprise New Delivery System
The new delivery system uses a combination of three
compoundsligands, p53, and liposomesin a carefully
developed ratio to produce a small enough structure to penetrate into
the small blood vessels in the tumor cells. Either folic acid or
transferrin is used as the ligand since both are highly recognized by
tumors and can attach easily to tumor cells.
The p53 gene is enclosed in a liposome, which, in turn, is attached
to the ligand, and the combined entity is released into the blood to
find its way to the cancer cells. When normal p53 is reintroduced
into the cancer cells, these cells become more sensitive to common
chemotherapy drugs and radiation therapy, thus destroying more of the tumor.