Killing Cancer With a Virus

just___giver writes "The U.S. National Cancer Institute has just decided to fund multiple human clinical studies to test the reovirus. This naturally occuring virus has a remarkable ability to infect and kill cancer cells, without affecting normal, healthy cells. Here is a before and after picture of a terminal patient with an actively growing neck tumour that had failed to respond to conventional treatments. This tumour was eliminated with only a single injection of the Reovirus. Researchers at Oncolytics Biotech have shown that the Reovirus can kill many types of cancer, including breast, prostate, pancreatic and brain tumours. Human clinical trial results indicate that there are no safety concerns and that the reovirus shrinks and even eliminates tumours injected with this virus. Numerous other third party studies show that the reovirus should be an important discovery in the treatment of 2/3 of all human cancers."

good...

[mantera]

i find these as very very welcome news, especially so that i have personally seen the effects of conventional therapies; if you're lucky you'll have a tumor they can cut out, if not then too many of those chemotherapies are way too toxic, and quite a few radiotherapies too.

Clarify

[forand]

It seems people think that we made this virus, if you go to the link [oncolyticsbiotech.com] in the overview you will see that:

3. What is the reovirus Reovirus stands for Respiratory Enteric Orphan Virus. The reovirus is a naturally occurring virus to which most of us have been exposed in our lifetime. It is a non-pathogenic virus, meaning that it is not usually associated with any illness. Between 70 and 100 per cent of the population show signs of previous reovirus infection, which is usually confined to the respiratory or gastrointestinal systems in the body.

4. Where does the reovirus come from? Reovirus is found naturally in shallow pools of water, lakes or streams or in the sewage system.

Hope this clarifies things.

Re:How do they know?

[Anonymous Coward]

This is a virus that exists in the wild. It's not some sort of designer human pathogen. In the family of reoviruses are enteroviruses such as rotavirus, the most common cause of diarrhea in children.

Re:good...

[conteXXt]

Inhibition of tumor angiogenesis by cannabinoids.

Blazquez C, Casanova ML, Planas A, Del Pulgar TG, Villanueva C, Fernandez-Acenero MJ, Aragones J, Huffman JW, Jorcano JL, Guzman M.

Department of Biochemistry and Molecular Biology I, School of Biology, Complutense University, Madrid, Spain.

Cannabinoids, the active components of marijuana and their derivatives, induce tumor regression in rodents (8). However, the mechanism of cannabinoid antitumoral action in vivo is as yet unknown. Here we show that local administration of a nonpsychoactive cannabinoid to mice inhibits angiogenesis of malignant gliomas as determined by immunohistochemical analyses and vascular permeability assays. In vitro and in vivo experiments show that at least two mechanisms may be involved in this cannabinoid action: the direct inhibition of vascular endothelial cell migration and survival as well as the decrease of the expression of proangiogenic factors (vascular endothelial growth factor and angiopoietin-2) and matrix metalloproteinase-2 in the tumors. Inhibition of tumor angiogenesis may allow new strategies for the design of cannabinoid-based antitumoral therapies.

PMID: 12514108 [PubMed - indexed for MEDLINE]

Re:Resistance

[Baron_Yam]

I may be out of date in my medical knowledge... but I'm pretty sure cancers can only develop an immunity in a single person over a course of treatment, and can't spread like a virus or bacteria to other people carrying the acquired immunity with it.

After all, cancers aren't transmitted between people, they spontaneously appear for a variety of reasons.

Re:How do they know?

[TheWhaleShark]

Typically, virii (or viruses, whatever) manifest their effects realtively quickly, due largely in part to the nature of the virus life cycle.

In addition, if the virus only responds to the receptors found on cancer cells (which is, I imagine, how it works), then there is next to no chance of it ever infecting normal healthy cells.

Though, I agree...this should be studied for a couple of more years, just to be on the safe side. However, I'm nigh positive that this could lead to a definitive cancer cure.

Re:How do they know?

[denisonbigred]

But ethically dubious experiments in which prisoners were injected with reovirus found that infection caused at most mild flu-like symptoms. Many people have been infected by reovirus as children with little effect more than a runny nose.

That text comes from section 3 of this [uwaterloo.ca] article. So it would seem that the answer to your question was determined quite some time ago.

Re:But...

[AlaskanUnderachiever]

It "partially" works because you have antibodies to the virus already. Your body recognizes the particles of virus as a "bad guy" and while the virus tends to attack the tumor cells, the body itself is eliminating the virus and any tumor cells infected with it.

However, it appears that the virus itself is fairly effective at killing of tumor cells on it's own which is fairly interesting. As it's not associated with any pathogenesis this is definately an interesting step.

Yes you can get infected more than once, hell you can get reinfected over and over again. If you have antibodies it'll probably be a fairly asymptomatic infection (pardon my spelling).

Geneticly Modifed Virus ...

[Anonymous Coward]

Read carefully ...

"its proprietary formulation of the human reovirus".

Re:Not so fast buckwheat!

[denisonbigred]

Yes, but this research was started before the formation of the biotech company which now holds the rights and has been pretty well documented, so that seems a bit unlikely to me.

that's why they have

[The Tyro]

Compassionate use protocols for some drugs... for people who are terminally ill and have nothing to lose by trying risky, untested drugs.

They've been using this in HIV patients for years. The only reason I could see them being more hesitant to treat cancer patients in a like manner is this: there ARE treatments for cancer that are curative... most all the treatments for HIV simply buy time... they do not eliminate the disease. Chemo is extraordinarily unpleasant, but it does have a proven track record...

Re:Okay, lets try it then...

[pvt_medic]

Here is info about FDA clincical drug testing policy. Phase 1 = This is the initial test in humans for safety. This phase is to rule out inherently dangerous drugs that were not caught in the animal tests. Since we are different species this is absolutely necessary. Of course, some medications were ruled out in the animal phase which might have worked very well in humans. Common aspirin fits this picture. Aspirin causes abortions of mice and rat fetuses. Under todays rules aspirin could never reach the human testing stage. Phase 2 = This is the efficacy trial. To make sure it does what the drug company claims. This and Phase 1 are usually small numbers of people. Phase 3 = This is the large test and currently obesity control medicines are required to turn in 2 years of data. All other medications are required to turn in a one year study. This tests how the drug will act in long term usage. Earlier tests usually were for only one to three months in duration. What is the best way to use the medication? This is the last Phase before FDA marketing approval. After this phase the studies conducted by the companies and others are given to a subcommittee of experts to review. If the subcommittee reviews and approves the medication it is passed to the FDA for final approval. Usually the full FDA committee follows the panel of experts advice. CLINICAL TESTING IN HUMANS Number of Patients in each study Length of study Purpose of study Percent of Drugs Successfully Tested Phase 1 20-100 Several months Mainly safety 70 percent Phase 2 Up to several hundred Several months to 2 years Some short-term safety, but mainly effectiveness 33 percent Phase 3 Several hundred to several thousand 1-4 years Safety, effectiveness, dosage 25-30 percent Marketing = After final approval by the FDA the medication is manufactured and distributed to pharmacies and physicians. It is then available for you to use. One pharmacist said the process takes about 6 weeks after final approval. Another source said it can take up to two years. Phase 4 = Any after-market studies recommended by the FDA or performed by the companies. This is where we go from having a few thousand people take the medicine to having millions of people taking it. And this is where any very rare side-effects may show up.

Re:How do they know?

[sosume]

When you are trying to fight cancer with an adenovirus, like a particularly nasty common cold, you get a mutated adenovirus that seems to copy itself only in cells that lack a functioning copy of a gene called p53 that repairs damaged or mutated DNA. If the DNA is then too smashed up to be repaired, p53 instructs the cell to self-destruct. Since cancer occurs when DNA becomes so badly battered that it stops regulating cell growth and behavior, it is not surprising p53 has stopped working in more than half of human tumors..

Re:How do they know?

[martyros]

In addition, if the virus only responds to the receptors found on cancer cells (which is, I imagine, how it works), then there is next to no chance of it ever infecting normal healthy cells.

Actually, the FAQ linked to by the article has a very simple description of how it works:

6. Why doesn't the reovirus infect normal cells?

It enters normal cells, but when this happens, an anti-viral response mechanism is turned on and the virus is quickly eliminated. Anyone injected with reovirus is usually able to clear it completely from the body in about two weeks.

7. Why does the reovirus kill cancer cells?

Scientific studies have demonstrated that approximately two-thirds of all human cancer cells have an activated Ras pathway, one of the most common set of mutations leading to cancer. An activated Ras pathway leads to a constant barrage of growth signals to the cell, causing uncontrolled growth. In cells with an activated Ras pathway, the anti-viral response appears to be turned off. When reovirus infects one of these cancer cells, it is able to replicate and eventually kill the cancer cell. Up to 5,000 progeny virus organisms can then infect and kill surrounding cancer cells. Theoretically, the cycle of infection, replication and cell death will continue until there are no longer any cancer cells accessible.

So in fact, it can and does infect normal cells; but it's so weak that it never causes any problem. Elsewhere on the FAQ it says that most humans show evidence of having been infected by it at some time (it's a naturally occuring virus).

Re:How do they know?

[SmokeSerpent]

RTA

3. What is the reovirus
Reovirus stands for Respiratory Enteric Orphan Virus. The reovirus is a naturally occurring virus to which most of us have been exposed in our lifetime. It is a non-pathogenic virus, meaning that it is not usually associated with any illness. Between 70 and 100 per cent of the population show signs of previous reovirus infection, which is usually confined to the respiratory or gastrointestinal systems in the body.

6. Why doesn't the reovirus infect normal cells?
It enters normal cells, but when this happens, an anti-viral response mechanism is turned on and the virus is quickly eliminated. Anyone injected with reovirus is usually able to clear it completely from the body in about two weeks.
Back To Top

7. Why does the reovirus kill cancer cells?
Scientific studies have demonstrated that approximately two-thirds of all human cancer cells have an activated Ras pathway, one of the most common set of mutations leading to cancer. An activated Ras pathway leads to a constant barrage of growth signals to the cell, causing uncontrolled growth. In cells with an activated Ras pathway, the anti-viral response appears to be turned off. When reovirus infects one of these cancer cells, it is able to replicate and eventually kill the cancer cell. Up to 5,000 progeny virus organisms can then infect and kill surrounding cancer cells. Theoretically, the cycle of infection, replication and cell death will continue until there are no longer any cancer cells accessible.

Re:Surgical strike medicine

[gurps_npc]

Did you read the story? This is an all or nothing approach. You infect the entire patient and hope the virus will only kill the desired cells. If it turns out that the virus kills your healthy cells instead of the tumor, you die.

Radiation on the other hand is far MORE of a surgical strike approach. The radiate just the tumor area, not the entire body.

Re:Calgary builds Cure for Cancer

[Anonymous Coward]

There's a really fun computer game called Civilization 3. You should play it sometime.

Re:Okay, lets try it then...

[Planesdragon]

Waivers be damned, because whenever you beleive something is unthinkable, there is always someone out there who thinks they are entitled to something.

You're obviously not familiar with the law, at all.

There are very clear doctrines in many states regarding Assumption of Risk. So long as the doctor makes it very clear to the patient that the cure is only possible, and it there might be outrageous side-effects anyway, the doc should be fine.

Unless, of course, the doc lied / misrepresented facts to get a new treatment tested--in which case, the doc should pay.

Re:old soviet PHAGE technique

[soma]

Phages are viruses that attack bacteria, not the cells of our body. The "old Soviet research" is an alternative to antibiotics, not a type of cancer therapy.

This startup is using a naturally-occuring virus to kill cells with compromised anti-virus defenses. It just so happens that many cancer cells are so compromised.

Neat work! But definitely not the same.

--Anil

Slashdot editors: still asleep at the wheel.

[Doktor Memory]

Blatant astroturfing: this article is hyping a completely unproven treatment, and was written by an employee of the company. This is news? Every biotech company has a "promising" anti-cancer treatment in development.

Re:Okay, lets try it then...

[Tim C]

That may well be true, but just because the "doc should be fine" (emphasis mine) doesn't mean that the hospital/clinic and/or manufacturer of the drug won't be forced to defend against lawsuits anyway.

Even the thought of having to defend against such a suit may well be enough to stop a lot of places from doing this. Such a waste.

Re:good...

[CrackHappy]

I had cancer. Thank God they were able to cut it out. I can't stress enough the importance of getting your ass to the doctor if you even suspect something is wrong. All you young men out there, listen up. Testicular cancer is MOST LIKELY to strike between the ages of 25-35. Also note, 98% of ALL masses detected in testicles are cancerous. In other words, when fondling yourself, if you notice anything weird at all, especially anything hard, get yourself checked by your doctor ASAP. Also note Testicular cancer is one of the fastest spreading cancers, but also the easiest to cure, IF it's caught early enough.

The treatment sucks, but it's better than dying!

Re:Okay, lets try it then...

[Walter Wart]

There are many other concerns among them are:

1. How much of the experimental agent do you have? These things are often expensive, rare and certainly not covered by insurance
   
2. You have to pick your subjects carefully if you want to get useful results. The point of a study is to study.
   
3. There are compassionate exemptions. Later posts by "The Tyro" go into these in great detail.
   
4. Liability. How do you guard against lawsuits if the treatment has unforseen side effects? Waivers can be fought.
   
5. By the time a person is terminal he or she is often not a good candidate for a haircut much less an experimental drug or procedure. Getting back to the limited supplies and "do no harm" principles someone has to decide whether the experimental substance is better given to someone who has a better chance of survival.
   

Speaking personally, I just underwent surgery and am awaiting radiation for a tumor. I would have much prefer to have gotten an injection, a severe cold, no tumor, and the continued use of an important body part. But I was not selected for such a study and couldn't have paid for the drug anyway. Such is life. I am just glad that my prognosis is good and hope that the virus will be approved as soon as is scientifically appropriate.

Re:Surgical strike medicine

[CoreyGH]

I don't think YOU read the story.

Reovirus stands for Respiratory Enteric Orphan Virus. The reovirus is a naturally occurring virus to which

most of us have been exposed in our lifetime. It is a non-pathogenic virus, meaning that it is not usually associated with any illness. Between 70 and 100 per cent of the population show signs of previous reovirus infection, which is usually confined to the respiratory or gastrointestinal systems in the body.

And you don't infect the entire patient if you can get at the tumor:

8. How is reovirus administered to patients?

Reovirus is being injected directly into cancerous tumours in our T2 prostate and glioblastoma cancer studies. Oncolytics has also completed the preclinical work required to begin a systemic study, where the reovirus will be administered intravenously.

Re:Slashdot editors: still asleep at the wheel.

[Dave21212]

You hit that one on the head... It's a company PR release no less. Interesting, but definitely astroturf.

From the ONCY Yahoo Stock message board [yahoo.com]...

slashdot submission ??? need help

by: just_9_giver
Long-Term Sentiment: Strong Buy 11/03/03 06:12 pm
Msg: 5822 of 5871
(response to RJC's question)
I'm thinking its time to submit a summary with good links to http://www.slashdot.org

With luck, it'll get 15 minute of fame in geekdome. Every news writer of any substance reads this site. It might even show up on Google's news page right away.

The trick is to get a good story submission. It should have one link that points to a recent article. I was thinking the NCI article would be appropriate

Any tips for links and a couple of paragraph summary? Probably easier to collaborate on this rather than try to come up with it all by myself.

Posted as a reply to: Msg 5817 by rjc2827

Re:Slashdot editors: still asleep at the wheel.

[signe]

Just because the guy posted to the Yahoo message board before posting to Slashdot doesn't mean he's a PR flack, or that this is astroturfing. And that he wanted some help with putting the submission together points even more towards someone who is not associated with the company.

-Todd

Re:Okay, lets try it then...

[Anonymous Coward]

In Scientific American, their article shows a picture of a 19 year old kid who died from a bad reaction from the virsuses he was being treated with. The teen and his family knew the risks, and the took it, and no one got sued.

Re:Okay, lets try it then...

[CritterNYC]

Here in America that doesn't happen either.

Here's some interesting reading: OverLawyered.com [overlawyered.com]

It's not just Reovirus:

[Momomoto]

The lab at which I'm doing my Honours research project just made the front page [cancercell.org] on October's issue of Cancer Cell [cancercell.org] for doing work similar to this, only using vesicular stomatitis virus. The group on the lab bench across from me is working on oncolytic adenovirus.

It's shameful that the companies who make the most press releases get the most attention.

Astroturfing is right

[Anonymous Coward]

Gee, reovirus will CURE CANCER! And Longhorn will CHANGE YOUR EXPERIENCE on the INFORMATION SUPERHIGHWAY!!!

As Doktor Memory said, the post contains no links to substantive biology articles, no discussion of the long and checkered history of attacks on the Ras pathway, and little information about what is actually going on. If you want real information go look at the PubMed on 'reovirus ras' [nih.gov].

It'll be great if reovirus increases survival rates in Ras cancers, but it will not be a magic bullet and it could easily fail final clinical trials for one reason or another. It just ain't over 'til it's over in the pharmaceutical industry.

Re:Physician perspective

[seafortn]

Can you give any proof of the link between IRBs (or HSCs) and the AMA? Since IRBs exist at institutions to review reseach done at institutions, it would stand to reason that the people submitting proposals on research done on humans to the IRB would, in fact, have degrees, since they work there. Since this applies t all human research, psychologists, too (for example) have to get IRB approval - and I don't believe that most sports physiologists (another example) or psychologists have anything to do with the AMA. Since the IRB exists to prevent research that harms the subject, like the Tuskegee experients, for example, I am puzzled by your assertion that it exists to drive up health care costs. Can you please clarify or give any proof? Thanks!

It's only Phase II, not ready for prime time

[nbauman]

This work is scientifically very interesting but it's a long way from curing cancer.

On the Oncolytics web site, they only list Phase I and Phase II trials. That's just to evaluate safety and dosing. In Phase III, they finally get around to testing for effectiveness, and they haven't done that yet.

I've seen lots of drugs that did this well in Phase II trials but flunked Phase III. I remember seeing Fortune magazine with the headline on the cover, "Cure for Cancer!" 20 years ago. Unfortunately not. (They got over-enthusiastic about cancer vaccines.)

Phase III is a randomized controlled trial. They randomly assign half the patients to the drug, and half the patients to a placebo. If it really works, you should see the difference. A lot of times it doesn't work and you know the drug is useless. Until the RCT you don't know anything for sure.

Another distinction you have to make is the end point. It's one thing to shrink a tumor, but the main thing most cancer patients are interested in is whether they're going to die. There are a lot of drugs that shrink tumors, but have no effect on how long they live.

Here's a discussion, "Levels of Clinical Evidence in the Primary Literature" [uic.edu]which describes the different levels of evidence. Or look at BMJ [bmj.com] Or if you want to search Google look for "Evidence-based medicine."

I hope this will encourage investors to throw lots of money at basic research and give us a better understanding of why cells become cancerous. It makes the New England Journal of Medicine more fun to read. Who knows? Maybe they'll come up with something useful some day. But not today.

Avg Life expectancy

[petronivs]

Back then, the average life expectancy was so low because of infant mortality. People who got to puberty didn't, on average, die much younger than people do nowadays.