"What's exciting is we may now be able to design a therapy that will seek out and destroy only cancer cells," said the study's senior author, Paul B. Fisher, Ph.D., professor of clinical pathology and Michael and Stella Chernow Urological Cancer Research Scientist at Columbia University Medical Center. "We hope it will be particularly powerful in eradicating metastases that we can't see and that can't be eliminated by surgery or radiation. Gene therapy, especially for cancer, is really starting to make a comeback."
The virus's selectivity for cancer cells is based on two molecules called PEA-3 and AP-1 that, the researchers found, are usually abundant inside cancer cells. Both of the molecules flip a switch (called PEG) that turns on the production of a cancer-inhibiting protein uniquely in tumor cells.
The researchers say the PEG switch can be exploited to produce gene therapies that will only kill cancer cells even if the therapy enters normal cells.
As an example, the researchers constructed an adenovirus that carries the PEG switch and a toxic protein. The switch and the protein were connected to each other so that the deadly protein is only unleashed inside cancer cells when the switch is flipped on by PEA-3 or AP-1.
When added to a mix of normal and prostrate cancer cells, the virus entered both but only produced the toxic protein inside the cancer cells. All the prostrate cancer cells died while the normal cells were unaffected.
The same virus also selectively killed human cancer cells from melanoma and ovarian, breast, and glioma (brain) tumors.
This approach is important because cancer can not be cured without the development of therapeutic agents that have far greater ability than current conventional chemical chemotherapy agents to selectively target cancer cells while leaving normal cells unharmed. The use of molecular switches that will flip on to deliver therapies only in cancer cells is going to be one of the major ways that cancer is going to be defeated and perhaps even ultimately the best way. There are two parts to such a therapy. The first is the switching part that detects unique signature patterns in cancer cells to know to activate. The other part is what will get done once the activation of the switch has happened. There are many possibilities for the second part. Imagine, for example, an enzyme that gets synthesized in cancer cells that can metabolize inert chemotherapy compounds into toxic forms. Or imagine a protein made from the switch that effectively punches a hole in a cell. Or perhaps the switch would turn on a bigger package of genes that would restore normal cell division regulation. The gene package could include a replacement non-mutated p53 cell divisiion regulating gene to replace the mutated p53 genes found in many types of cancer.
Update: After watching a lecture by Judah Folkman on anti-angiogenesis compounds to control cancer a thought occurs me: What would be neat would be a gene therapy that turns on anti-angiogenesis genes only in cells that are cancerous. Then anti-angiogenesis compounds would be produced in an area of the body only as long as cancer cells were growing in that area. Or imagine a gene therapy that only in cancer cells would make RNAi (RNA interference) segments against the messenger RNA for VEGF and other angiogenesis molecules.
There would be a distinct advantage, however, to a gene therapy that just killed all the cancer cells and even the pre-cancerous cells. A cell killing therapy would have the benefit of also being a rejuvenating therapy since it would wipe out a lot of damaged cells and therefore provide healthier cells room to grow. Depending on what internal conditions of a cell were used to activate the gene therapy it would be effective even in cancers that have not mutated to the point of being able to develop new vasculature. So evenl the very small (less than a millimeter) cancers (that most people die with undiagnosed) could be wiped out. Given that those damaged cancerous and precancerous cells are not doing their original jobs well (if at all) and are likely to be releasing inflaming molecules and/or free radicals one can expect a rejuvenating benefit from such a treatment.
|Share |||Randall Parker, 2005 January 25 03:13 PM Biotech Therapies|