January 25, 2005
New Gene Therapy Selectively Kills Only Cancer Cells

Columbia University researchers have developed a gene therapy that is selectively toxic only in cancer cells.

"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.

Also see my previous posts "DNA Nanomachine Computers Against Cancer" and "A Couple Of Novel Cancer Therapies Reported".

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

Invisible Scientist said at January 26, 2005 8:19 AM:

How soon can this therapy be approved by the FDA?

Also, I wonder if there is a long term danger in this therapy, in the sense that the new
genetically engineered virus will probably be lurking around for many years, and can it later
mutate and become such that it will also start harming healthy cells after the patient recovers?
(And if so, can there be an epidemic of this mutated virus?)

Robert Silvetz said at January 26, 2005 12:34 PM:

The most optimistic scenario given current insane FDA regulatory guidelines -- 8 years.

On mutation damn good question, but probably not.

On epidemic, positive zero chance.

Invisible Scientist said at January 26, 2005 12:51 PM:

But if technology becomes so advanced that it is possible to manufacture a new
virus that can create poisons on specific types of cells, then it is almost certain
that the same methods can be used malevolently to create contagious viruses that
deliver deadly toxins to any foreign nation, and the enemy nation would, of course,
have the vaccine.

Robert Silvetz said at January 26, 2005 4:17 PM:

I get it. I was thinking narrowly in terms of the treatment.

If it is any consolation, we (and the Russians) have manufactured supergerms going on 40 years now.

But sure, hell, just make a virus for overexpression of TNF, IL-1, and watch everyone melt into a pile of feverish goo...

David A. Young said at January 27, 2005 12:21 PM:

"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."

Errr . . . that's "prostate," not "prostrate." I checked, and the error was in the original.

Randall Parker said at January 27, 2005 12:31 PM:


Is it acceptable usage to fix spelling errors in text that you are referencing from elsewhere? I see errors fairly frequently in stuff I'm thinking of linking to. I see [sic] inserted by those quoting from some source (or should the sic be parenthesized?). I never know what to do about it.

Bob Badour said at January 27, 2005 4:08 PM:

"the enemy nation would, of course, have the vaccine."


David A. Young said at January 28, 2005 2:13 PM:

Randall -- It's probably better just to point out the error rather than correct it yourself. It's possible you could unintentionally step on somebody's toes by doing the latter. And sic in brackets -- [sic] -- is the generally accepted form to use when you want to acknowledge that you're quoting something that you believe to contain grammatical/spelling/usage errors. And you're right, you could spend half your life doing it, if my observations are any indication. I generally reserve it for really egregious or obvious errors. I actually went to the EurekaAlert website to attempt to point out this rather embarrassing gaff, but couldn't find any means to do so. Oh, well.

Tj Green said at January 30, 2005 3:14 AM:

The word is similar to the gene.Both carry information,and both have more than one meaning,but it is the copying errors that bring about new life and new languages.We are an infinity of errors directed by interactions.It is good to see that one of these interactions(the virus)is working for us instead of against us.

k.shalini said at March 19, 2008 12:04 AM:

i came to know that even a healthy human being possess oncogenes which on exposure 2 certain conditions wil start their pathogenisis leading to cancer.my idea is if we all possess those genes before only means y cant we go for prophalaxsis like tetanus, polio vaccinations etc which we r givig 2 a new born baby for their irradication.as we all know *PREVENTION IS BETTER THAN CURE*.why cant we go for it.;

k.shalini said at March 19, 2008 12:28 AM:

u mentioned dat the adeno viruses wil enter into both normal as well as carcinogenic cells.wat wil be the fate of virus in normal human cell.how it wil get eliminated.

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