Oncological Virus, or OV. Pushing science fiction. But did Washington Post forget to mention the 2nd patient they released data on, who didn't have any kind of prolonged response?
The paper presents 2 cases, selected because they were the first 2 cases to be tested at maximum viral load. There are additional people in the trial, and they will release full results once they are available.
It included two slides showing before/after blood levels and imaging. They talk about how they modified the virus to emit a tracking signal, and how they modified it to target the cancer cells. Really, really mind blowing and impressive work. I would love a tour of that lab.
These are end-stage patients for whom everything else has stopped working. One of the patients had already undergone several experimental treatments. There is some really exciting research going on for MM (multiple myeloma) treatments, and maybe even cures.
I think this is one example of the free market working well. Typical MM treatment runs about $60k / year, and with recent developments, patients are living 10+ years. Total number of MM patients is increasing both because the disease is becoming more prevalent, but mostly because people are living so much longer with MM. In short, it's a large and growing market. But it's not a cancer you can treat and have it go into remission. You get on treatment, and you stay on it and keep those levels down. The typical treatment is biweekly therapy.
But these OVs are one-time deals. So a single dose treatment is a very interesting alternative. The only problem is, MM is extremely resilient, and the cells are everywhere. It's so hard to eradicate, unless the OV is a cure, it's just another tool in the box to manage MM and extend lives.
> I think this is one example of the free market working well.
How so? While I'm sure the Mayo Clinic will be attempting to patent and license this therapy, the research was apparently funded by the US government and various philanthropies.
[Quoting relevant sections of the paper since the full text is paywalled.]
"Grant Support: This work was supported by funds from the National Institutes of Health/National Cancer Institute (grants R01CA125614 and R01CA168719), Al and Mary Agnes McQuinn, the Harold W. Siebens Foundation, and the Richard M. Schulze Family Foundation. The National Cancer Institute RAID (Rapid Access to Intervention Development) Program supported MV-NIS manufacture and toxicology/pharmacology studies.
Potential Competing Interests: Drs Russell, Federspiel, and Peng and Mayo Clinic have a financial interest in the technology used in this research."
A solid point -- though the therapy is interesting on a novelty scale, the funding is decidedly vanilla. Grants fund the early research, patents are filed for novel findings, and if the therapy holds up eventually a large pharmaceutical firm will be necessary to perform the large scale trials.
Slightly tangential, but I wonder where the IP in this discovery is? If there is nothing to sell but injecting cancer patients with standard lab-grade measles, I think it is particularly open to being copied. Granted the measles used is genetically tweaked, but nothing I believe to enhance the therapeutic effectiveness.
I don't really know any hard numbers, but you have to imagine, getting this OV to market would be extremely expensive. Public funds only cover a small portion of the costs of the early research. Large scale phase 3 trials will be funded by the drug company expecting to profit off it.
If public funds and private donations could actually cover the research costs getting all the way to FDA approval, I would think you would see more doctors and researchers creating nonprofit partnerships to attract the funds and do the research. Sounds like it would be a dream come true to be funded to do research you cared about and better the lives of millions without the corporate suits getting in your way. But I think the reality is the facilities alone cost hundreds of millions if not billions, so just for Mayo to give you the lab space to work for a couple years is a major investment.
Public funds will end up paying for a large portion of those phase 3 trials because the biggest customer of the those drug companies will be government programs. If the trial is not successful that the government will still pay a large portion via increased prices for other drugs. (Plus there's forgone income via the extensive tax subsidies for health care spending.)
I don't know why we go through this kabuki process of pretending there is a functioning market in places where the government is such a dominant player (see also defense contractors). Why not just cut out the middleman?
I don't believe public funds pay for any large-scale, randomized Phase 3 trials in oncology -- the cost can rise above $100 million per trial! The overhead in terms of patient registration and follow up require the staffing, technology and expertise of a large pharmaceutical industry. And once that step is mandatory (again, in most large Phase 3 trials, exceptions made for pointed therapies like Gleevec), "the market" is necessary, functional or otherwise.
At this point I risk conflating not just two but three arms of the government: the NIH (funding), FDA (approval), and Medicare (payment).
> Why not just cut out the middleman?
Medicare has hinted at doing this, using its purchasing power to drive down the cost of drugs and refusing to pay for treatments approved to work but who have a low cost-to-efficacy ratio. A recent example is the fight over Hepatitis C medication[0]
Sometimes Walmart goes to a manufacture and says "We want to buy all of your output for the next 3 years, here's exactly how we want you to modify the product, and here's the quality assurance tests you need to do. Here's what we are going to pay." Walmart pays them some percentage up front and then over time as product ships and sells.
If I understand your analogy correctly, Walmart is Medicare, and the manufacturer is a drug company? If so, then said QA testing is not a guarantee; you cannot design a drug that will extend the lives of patients with end-stage cancer like you design a grill. It'd be like there was a government agency that compared the manufacturer's new grill to all other grills on the market, and only let the manufacturer sell theirs if it had a clearly defined benefit over the others.
I guess I didn't make my point clearly enough either time.
The government pays for the early research, sets all the ground rules for the drug trials, and -- as the drug companies' biggest customer -- ends up ultimately shouldering much of the cost of those trials whether successful or not. The government certainly has the financial wherewithal to fund stage 3 trials, $100M a pop is a rounding error on federal spending or even on just federal medical spending. So why not just go ahead and do so? Why the farce with pretending there's a healthy drug market when the government is driving so much of the process? Let's just admit this is a market failure of the public good variety, like firefighting and roads, and have the government provision it.
My dad has been a MM patient for close to 6 years now and you are spot-on about the disease's general behaviour..
We started with Lenalidomide and was on it until end of last year with breaks of up to 6-8 months where there was no specific meds.. He's now on a Bortezomib cycle which will end in a couple of months and we hope to have some months free of meds again..
We never did the bone marrow transplant considering his age and stress/recovery he would have to go through.. MM is sympathetic in the sense that people who respond to meds can have a high quality of life even while undergoing treatment (my dad is still a practising medical Doctor). Lenalidomide is a tablet that you take at home while you go in once every week or two for Bortezomib shots.. The treatment is also considerably cheaper in India (still not inexpensive by any measure)..
The overarching fear for MM patients is the fact that its indeed incurable and how far/long we can go on before running out of treatment options.. Personally, seeing such trials and success gives us hope and comfort.. OV looks a promising approach and I hope my dad and others will be able to benefit from it..
Sorry to hear about your dad's illness. MM is a bitch.
If coming to the US is an option, there is a treatment center (Myeloma Institute for Research and Therapy MIRT) that is part of the University of Arkansas and is probably one of the best places in the world to get myeloma treatment. I know quite a number of people that have gone there and gotten good results.
It is based in Little Rock (of all unlikely places) I think because it was founded by a grant from Sam Walton, founder of WalMart. He died from MM in 1992.
> But did Washington Post forget to mention the 2nd patient they released data on, who didn't have any kind of prolonged response?
They mentioned the second patient in the article:
The trial included two patients. Russell said the treatment worked in Erholtz, whose tumors were mostly in her bone marrow. However, it was unsuccessful in the other patient, whose tumors were mainly in her leg muscles, the Star-Tribune reported. He said more research is needed to know how the nature of the tumor affects the virus.
In the video at the mayo clinic site they talk a bit more about patient 2. While not all tumors were destroyed, they were fully mapped due to compounds from the thyroid being attached to the virus, implying that localized treatment would then be possible.
wait, what? I'm not an oncologist but I read that muscles are the one tissue or place in our body which does not get cancer - this has to do with the way muscles are so 'greedy' for blood vessels that they do not allow angiogenesis to cancer cells.
All haematological cancers are everywhere. The bizarre thing is, despite their outrageously disseminated nature, many haematological cancers now have amongst the best prognoses (at least in certain age groups).
If you take a look at the list of new MM therapies hitting the market in just the last 5 years, and the number that are in the pipeline, you can see there has been a surge of investment in MM treatments, when for years the only options were dex and ASCT.
I think all this investment has been bolstered by the market success that Revlimid and Velcade are seeing. These drugs are cheap to produce, sell for about $5k per weekly or biweekly dose, and that a large and growing number of people are very happy to pay for, because they are well tolerated for as long as they work. Revlimid is just a pill you take, Velcade is a shot in the arm, so both are very cheap to administer.
There is huge incentive to keep producing more of these MM treatments, because the MM becomes refractory to each successive therapy over time. If you can make a good first-line treatment which is effective for 3 years on average, that's more than $100k per patient, at what, 90% gross margin?
I don't mean "free market" in the libertarian sense. I mean it in the sense that investment capital follows investment opportunity, and we are definitely seeing that here.
I can't get past the fact that people almost certainly aren't paying for it. Insurance companies must be as very few could afford those costs. As many can't afford insurance, it's more like the free(ish) market. Thanks for your reply, I see what you mean now.
> But these OVs are one-time deals. So a single dose treatment is a very interesting alternative. The only problem is, MM is extremely resilient, and the cells are everywhere. It's so hard to eradicate, unless the OV is a cure, it's just another tool in the box to manage MM and extend lives.
Yes, the key point to watch next is to see if the MM does not come back after a couple of years.
One thing I don't understand is this attitude of "well we can't detect it, so job is done". I don't know the specifics of detectability, but presumably it means that n<N for some N. So there could still be some cells left. Why not throw every weapon in the arsenal at them, to ensure the cancer is completely gone?
EDIT, addendum: If you have a few treatments that each can kill 9999/10000 cancer cells. It seems the current approach is apply treatment a. Not detectable yay! They grow back to original numbers. Apply treatment b! etc. If you did them all at once, they wouldn't have time to grow back in-between treatments giving a larger chance you get them all.
This is correct. As a matter of fact, even dosing one chemotherapy may be a challenge for a patient if the side effects are too server (lowered immune resistance, can't keep food down, etc). We're talking about drugs with such small therapeutic windows that given too often can easily kill a healthy human.
That's general audience information that discusses treatments before and after surgery that are intended to work along with the surgery. If you click through to the various therapies, there is lots of discussion of combining them.
Great question. I've wondered the same thing for bacterial infections. Wouldn't it lower the risk of resistant bacteria developing to always use two different types of anti-biotics, so in case a few bacteria develop a resistance to one, they're still killed by the other.
This is much easier for bacterial infections vs cancer -- chemotherapy is (excuse the non-medical phrase) very close to actual poison. Antibiotics are very well-tolerated, so taking two at once is something that could be done and is indeed deployed in serious infections or when there is high risk of one.
This - nearly all antibiotics target parts of the bacterial cell that humans don't have. Antifungals have the problem that many of their targets are shared between eukaryotic fungal cells and our own. Chemotherapy agents have a huge problem in that they are targeting cells that used to be our own. It's a race between toxic to cancer cells and toxic to the rest of you.
Patient 1 did have a recurrence of a single tumor that was resolved with site specific treatment, though her marrow remained clear. I didn't see/hear anything about recurrence in patient 2.
The virus is gone from her system. The MM is not at undetectable levels. So unfortunately, this OV is not a cure. This particular patient, her MM cells aren't surging just yet.
I think the curative approach will ultimately come from immunotherapy, training the body to attack the cells. OV could certainly have it's place, for example as an alternative to ASCT.
>I think this is one example of the free market working well.
Well Fleming (who discovered antibiotics) was working for the (British) government, so if the above is in any way an indication of "the free market working well", then his extremely more important results were an example of public sponsored research working great.
Is there any likelihood that measles, or a similar virus we have held at bay with vaccination, was actively fighting cancer 200 years ago, thus pushing up the incident rates that apparently have gone up and dismissed with "well we weren't dying of cancer because we were dying of $INSERT_DISEASE_HERE"
It is not a silly question. We can put it through the paces.
The question you are getting at is, "Did measles evolve to keep cancer at bay?" Or stated in another way, "Did it evolve because it was keeping cancer at bay?" The 2nd question is more attuned to our understanding of evolution.
For this to be the case, cancer must have been killing a significant number of people before they reached the reproductive age. However, we know cancer rears it's face well passed people have reached reproductive age. For women, breast cancer the most common of them all becomes rampant post-menopause.
With this view point, it seems unlikely that measles was an evolved response to cancer. Because, this has been a hand waving argument it has not addressed the ratios required for an evolutionary response, i.e Is it possible that cancer was killing enough (however small) prepubescents and that gave measles a chance to evolve?
Or, could it be that there was a way milder measles like virus that people acquired (like the common cold virus) and lived with henceforth and that protected them from cancer?
There are many interesting questions that come up.
The viruses didn't have to evolve specifically to fight, it could have been a side effect. For example, maybe cancer cells make better viral hosts because of their unchecked metabolism. So the virus evolves to exploit cancer cells first, killing them in the process. Here the virus "cures" cancer by accident, with no interest in the fact that it extends the life of their host.
I'm not saying this is likely, I'm just pointing out that your restatement of the question is a lot more narrow than the original question.
That was by intention. Head on, the original question is less penetrable. The restatement is meant to emphasize that a symbiotic relationship between the host and the virus could drive the evolution. Cancer -- bad for host, virus takes care of cancer for selfish reason, host lives long giving virus opportunity to spread. Along this line, your example gives a possible immediate attraction for the virus. It is the immediate attractions that start off the relationships, to disastrous, neutral or beneficial long term ends.
It is even possible that different viruses could be fighting each other to get a piece of our cancer. Interesting stuff!
> For this to be the case, cancer must have been killing a significant number of people before they reached the reproductive age.
Evolutionary forces are still in play for people past their reproductive age, though admittedly in a much less direct way. A person that lives long enough to help care for their grandchildren will be more likely to have some of their genes survive.
Yes, particularly in a hunter-gatherer society (which all of us were until quite recently in evolutionary terms). In addition to caring for grandchildren, there's also the wisdom of age. It's only in recent generations that things have started changing so fast that this is devalued. For a long, long time having grandpa or grandma around to tell you where you could still find water in a once-in-a-generation severe drought, or what other things you could eat when the herds of food animals didn't show up that year, was very useful.
Looking at it another way, if old people weren't useful evolution would not have produced humans with such long lifespans after reproductive age (since the old people are consuming resources, populations where individuals died off shortly after the kids were autonomous would have had an advantage).
As I read it, in this case it's a specially modified version of measles that's used, not "vanilla" measles. Interestingly, the washington post write up also suggests that if the user had resistance to measles, another virus would have to be used.
This is what makes me skeptical about the possibility of the virus offering general protection. We have this immune system that provides us with protection from infection if we've already had measles, to the point that it will protect the cancer too. That means that unless you get measles for the first time while you happen to have cancer, it's not going to help you. So I suspect this didn't actually come up enough in nature to have a real impact.
True. For multiple myeloma, the average age at diagnosis is 65 years. However, there are more and more young patients each year. The youngest person I have seen was 18 years old.
It's unlikely, as most vaccine-preventable infections were diseases of childhood, so any selective pressure they put on other things in your body would take place well before most cancers develop.
It is however mathematically certain that the prevention of deaths from infectious diseases will drive up rates of death from other causes, as we have to die of something - the only question is what.
I am curious about the timescale of treatments for terminal diseases, and how trials can be morally randomised.
It seems to me that a very high percentage of people would opt for a potentially fatal, completely untested course of action as opposed to imminent death. So who gets to try these treatments, who tells dying patients they are not allowed them, and is there a black market or large amounts of money changing hands for experimental procedures?
Ekianjo in this thread quoted 7 years at the earliest for a treatment to become available. Surely with hundreds of thousands of desperate, dying, last chance sufferers, it is better to go to extreme measures and offer the most promising yet dangerous treatments to everyone. Is it simply a side effect of the way pharmaceutical companies have to do business? If so, it's sad, and maybe a larger share of cancer research money should be put towards 'out there' attempts to cure terminal patients.
Then vast majority of experimental treatments are worse than doing nothing. So, it's generally presented as your going to die either way would you like to help find a cure so the situation becomes less hopeless at some point in the future. However, in cases where there is a large demonstrated benifit they often end the contol and give everyone the treatment. Because extending lifespan by 10% is progress but you need a control the demonstrate it's actually better than random chance but a
10+x increase in lifespan needs no control.
PS: Wit is a great movie that deals with terminal illness from the patents perspective. If I recall correctly there is a vary minor subplot around a trial on the proper drug dosage. At no point is the idea that this might be a cure just possibility of slightly extending your lifespan at the cost of a lot of pain. It's basic cost/benifit analysis but taking higher doses is in no way presented as better.
disclaimer, I work on cancer drugs so I can shed some light on your question.
> a very high percentage of people would opt for a potentially fatal, completely untested course of action as opposed to imminent death. So who gets to try these treatments, who tells dying patients they are not allowed them, and is there a black market or large amounts of money changing hands for experimental procedures?
First, for many cancers you do not die of an imminent death. Sometimes it can take 5 to 10 years to die from Cancer.Unless you are affected by a cancer where no treatent is available, there are usually multiple courses of treatments you can follow before being out of options.So patients are actually trying existing methods before jumping to new treatments. New treatments are only available in small quantities and there are strict criteria for the selection of patients. And in Oncology actually we already give the chance for patients to try new drugs as soon as the safety evaluation begins, whereas for other therapies we go through healthy volunteers first. For a patient there is not much incentive to join Ph1 since the efficacy is not proven and there is a dose escalation method so you may not get the efficacy dose even if you enter the trial. Besides, there are safety risks involved and some patients die in Ph1. So every patient signs an informed consent that they are aware of the risks involved.
As for the hundred of thousands of patients, the companies cannot support them for many reasons: as mentioned, the drugs are only manufactured in small quantities in early stages and it takes years to scale up the process. Second, clinical trials cost a lot of money, and the more you have patients the more it costs. So you dont recruit more patients than what you need to do your evaluation. This being said, most pharma companies continue providing drug even after the trial is completed to patients who see efficacy with it. Third, the larger the trial, the longer the enrollment time and the longer it takes to get the results back and therefore the longer it takes before the drugs reach the market.
> Who tells dying patients they are not allowed them, and is there a black market or large amounts of money changing hands for experimental procedures?
The FDA regulates every aspect of clinical trial design. Dying cancer patients are always the first to receive untested drugs -- the FDA has set the bar that any new therapy must outperform what is currently used. There is no "black market" for experimental procedures, mostly because you must visit a hospital to receive them in the first place. Some drugs are intravenous; all are given with standard oncology examination. A doctor cannot write a prescription for a drug not on the market yet for you to pick up at the pharmacy!
> Surely with hundreds of thousands of desperate, dying, last chance sufferers, it is better to go to extreme measures and offer the most promising yet dangerous treatments to everyone. Is it simply a side effect of the way pharmaceutical companies have to do business?
In order for the testing of a Phase I trial to be complete, patients must meet certain criteria. The FDA (and, by extension, the pharmaceutical companies who want FDA approval) require enrolled patients in a clinical trial to have similar levels of disease. A patient that is clearly near end of life may not be able to physically swallow a pill...their outcome may bias the trial's results.
Yes, there are desperate and dying cancer patients, but a Phase I trial can (and should!) only accommodate dozens of them to achieve proper statistical power. Phase II may take hundreds, and Phase III will take even more -- but when a drug is approved, it has the possibility of being given to many thousands or millions of patients all at once.
As the trial population grows, medicine rears its stochastic side -- despite patients having pathologically similar disease, some will be helped and others will not. This is at the core of all FDA trial design: big populations are necessary to see just how effective your drug is. It should not be surprising, then, that the majority of failures happen at the bigger scales (PhII and PhIII).
When the treatment puts a large number of terminal patients into remission, there is no statistical reason for a placebo control. You know what percentage of such patients will die when offered a potentially revolutionary therapy that does nothing, because there are previous therapies that didn't work. If one third of your patients go into remission, one third show improvement and the treatment has no effect on one third, you know the treatment works better than a placebo.
As for offering this to desperate, last chance sufferers, unfortunately the history of potentially revolutionary cancer treatments shows this is a bad idea. If the treatment kills 90% of people within hours or days of treatment (sadly this is a realistic outcome before dosing is worked out and in some cases, regardless) then it is morally unacceptable to roll it out to thousands of people. You have to do the trials first to establish whether it works, is safe, that it doesn't cause unnecessary suffering and hasten death and what the optimal dose and protocol is. You also have to figure out how to deal with patients who do have an adverse reaction to the treatment.
I recommend to watch Dallas Buyers Club, it addresses the very point you make.
One could argue, how could the trials NOT be morally randomised? Are we doing a disservice by not conducting the trials in a way to study the efficacy of certain drugs.
It should be noted that one of the components to many drug and observational trials is the ability to halt the trial and switch patients on or off drugs as it becomes clear that one treatment is vastly superior.
The original studies of aspirin and heart disease were, for example, halted because the benefits were so clear that it wasn't considered ethical to keep the placebo arm untreated.
Several HIV trials have similarly been halted because the treatment was showing no or negative effects.
A third problem which hasn't been discussed: If a new treatment is hapharazdly applied and a lot of patients die from it, funding will dry up and continued research will stop. Not to mention that the US legal system would be a problem for the doctors involved. So the researchers who are at the front of developmenst like this are really cautious, which further slows the process.
It's valid morally. However, science runs on grant money and grant money will usually only be given to projects that show a proper scientific method. It would be nice if there were some sort of open market, where terminally ill patients could opt in to clinical trials. But these trials must be tightly controlled, or their results are meaningless.
I would argue that as a terminal patient, I certainly would not want to be part of the control group taking a placebo or no treatment at all, and that the scientific method could still be applied later when you still have a lot of people that took the treatment compared to a lot of people who didn't, for one reason or another. I imagine scientific grants could be funded on an individual basis, if the individual is rich enough.
Usualy placebo arms get less than 50% of the patients anyway. So most people on trials get the drug. And no, you cannot "apply the science later" because you specifically want to see the difference in PFS (progression free survival) and OS (overall survival) on both groups, and for it to be comparable they need to start with the same baseline.
But we're talking about people who have been told "this disease is going to kill you." If a treatment causes even 5 percent of them to be cured, how is that not significant? What if 40 percent have tumors shrink? Remember, any reversal of the disease is a good thing. If you're just measuring a statistical increase in life span (say 3 years treated vs 1 year placebo), I'd say you're not really aiming high enough. If you've got something with real promise you'd know it without a control group. The person in this article is exactly such a case.
It's more that the controlled placebo group will also be controlled for other medications that could compromise the research. If I have cancer A and I'm taking three or four medications + an experimental medication then it's difficult to know which factor affects the results. So the control group will be on the same types of medication in a proper study where as a sort of ad-hoc grouping of patients would be less easy if not impossible to accurately report.
I assumed we'd be comparing to the predicted outcome from no treatment, but I suppose if you wait until Hospice time there's not going to be much success with even the best virus compared to doing nothing. Which raises other questions about just how long and at what cost we try to delay the inevitable.
It's not just that. If it's not properly and exhaustively tested, then they open themselves up to litigation by people who recover less than 100% or who have a new symptom.
It's also worth noting that there is a constant sussurus of "miracle cure for foo!" that doesn't actually pan out in the long run.
The main problem with that is you will have a lot if nefarious groups abusing the situation. Desperate people will sign away their rights without understanding their risks. And even though they may already be dying, they can always suffer more. I fear this would lead to dangerous experimentations.
There is a long history of cases in which a patient with cancer has made a miraculous recovery following an infection, and especially with fever (cancer cells have massively disrupted heat shock proteins which are usually mutated into non-existence in the pathway to uncontrolled replication and loss of cell cycle regulatory proteins) - additionally, fever increases the function of immune cells.
The earliest case reports I remember date back to the 1600s and for a short time in the late 19th early 20th century there were doctors that practiced that way however the results seemed highly variable and generally fell by the wayside.
It is great to think that this might be true, there is certainly evidence to suggest it is somewhat credible but like anything we will require more evidence before we can claim that it 'changes everything'. We can always hope though.
- ps apologies for lack of sources, I'm on mobile, I'm a doctor working on an oncology ward and I just had my worst day in my 5 month long career today and hardly in the mood to do the research legwork required to substantiate my claims. Google will help - start with hyperthermia therapy if interested in going down the rabbithole
Thank you for the link, this is quite interesting.
If I may ask a stupid question, wouldn't this imply that cancer rates should be lower in tropical countries, where the ambient temperature is consistently >40°C ?
I've never heard anything like that, but you must remember that it is body temperature that is important and it is never normally above ~37.5
Thee is actually a really interesting paper, tangentially related, on sepsis (blood borne infections) which randomised ICU patients to have either aggressive temperature management (ie fans, active cooling and paracetamol) vs allowing the temperature to rise as high as 39.9. Although the study was small in size(I think there were roughly 15 in each arm) the 'permitted fever' arm had only 2-3 fatalities vs 14 in the aggressive fever management arm. I actually have that paper on my desktop and will dig it up
"Within the next several years, it is likely the technique will become a standardized treatment for cancers such as myeloma or pancreatic cancer, Tanios Bekaii-Saab, a researcher at James Cancer Hospital and Solove Research Institute in Ohio, told the Star Tribune. Still, the study must be confirmed in large randomized clinical trials.
“Unless we get to the third stage of development, we are cautiously optimistic,” he said."
Cautiously optimistic is the right wording. Seems like the patient has a severe reaction to the injection - if they get patients with even worse reaction or even dying from it, it could kill the therapy for good in Phase I.
Even if they get to Ph3, cancer trials usually take several years to enroll and to reach results, and it wouldn't be a therapy before 6-7 years down the road at the earliest, since you'd want to demonstrate PFS and OS improvement and that takes time in certain forms of Cancer.
EDIT: Patients experiencing complete remission is not completely exceptional in Phase Is. it happens, but it's usually very rare that it occurs in MANY patients. So, effectively speaking, this is n=1 datapoint at this stage, unless demonstrated otherwise.
You are thinking of allogeneic bone marrow transplants (bone marrow is transplanted from a donor) where there is a 20% chance of death. Typically, myeloma patients get autologous transplants (the patient self donates bone marrow stem cells) which are much less dangerous (less than 5% death rate). I know someone who has had five ASCTs (autologous stem cell transplants) and he is still kicking. It's not a cake walk but at least you don't die.
If they get to phase 3, that means the stuff probably works, and it means people really sick can probably get it via compassionate use. So that'd be good news.
The video that's included with the full text explains the study in layman's terms and is very accessible to the general public. Lots of good info there.
I see no reason why it isn't real, unfortunately a trial of 1 does not a cure make, however it does seem very hopeful, even if there is a long way to go with more extensive trials.
Statistically and probabilistically speaking, we can make an estimate (with error bars) of the value of the treatment, even with a trial of only a few people.
The first patient did have a recurrence of a single tumor that was treated locally, with her marrow remaining completely clear. The second patient had his marrow cleared and all but a couple tumors in his legs resolved. And the virus penetrated those tumors and allowed full 3D mapping of them due to tags attached to the virus itself (it sounded like a thyroid produced chemical was attached to the virus as a tag). The implication was that because of the detailed mapping that it would be possible to resolve/remove the remaining tumors in the leg muscles of the second patient.
So, the answer is quite a bit much more complex than 50%. Both patients cleared the myeloma from their marrow. Almost all (numerous!) tumors were removed, from a single treatment in each patient.
What happens if it turns out that the treatment is fatal in 30% of cases? A trial of 2 would not necessarily show this type of thing. That is why one cannot extrapolate this without much more information i.e. more trials.
nobody is saying that more trials are unnecessary. my point is to emphasize the limited data so far is compelling, and that it goes beyond a 'trial of 1'.
Virus therapy has been on the table for a long time in the cancer fight. Because we can manipulate a virus and have it deliver highly targeted attacks, the idea of destroying cancers while ignoring healthy cells is sort if the holy grail of cancer treatment research.
There isn't a single thing called "cancer". There are many many different types of cancer. What might work for one type might be helpless against all others.
But want to say that after a period where the definition of cancer broadened out to a multitude of diseases as you say, with the help of genetics I think it's starting to converge back - many different cancers work through similar genetic mechanisms. We're slowly starting to understand common themes that act broadly across many cancers. With the help of recent advances in sequencing people are finally getting a grip on tumor heterogeneity (something that was previously misunderstood) and it seems like across many cancers, we are starting to get a feel for how cancer responds in common ways to drug interventions, and why it can be so resilient and difficult to eradicate. So yes, lots of diseases, but underlying it all, there's a common genetic architecture.
I think this is unfair - obviously each type of cancer has unique properties but the general ontology, mode of operation and treatment options have enough overlap that it - in a single word - describes what an illness is in general.
“Cancer” is a very wide classification. It’s similar to classify the illness as “caused by bacteria” or “caused by virus”.
It’s not very useful to know only that you have a disease that is caused by a virus. It could be a common flu, melease, ebola, herpes, hepatitis, hiv, ... http://es.wikipedia.org/wiki/Virus#mediaviewer/Archivo:Viral.... Each one has a very different treatment and prognosis.
Some cancer would kill you in a month and some will kill you in 100 years (if you don’t die from other cause), some cancers are easy to operate, some are easy targets to chemotherapy, some for hormone therapy, some for radiation, ... A cancer diagnosis is a bad new, but it’s a very wide range of bad.
Also a new “cure” will probably be useful in a very few specific cases, and not useful in a general case like a broad spectrum antibiotic, that is useful against a lot of kind of bacteria.
Not, it would seem, a panacea. Approach is interesting in that aspects of cancer biology make the cells more vulnerable to viral infection, eg supressed interferon production. Also a possible platform for immunotherapy ie getting the immune system to attack a virally infected cancer cell might wake up a more generalised immune response. But, medical grade virus is expensive to produce, and hard to think how a viral infection could eradicate 100% of the billions of cancer cells present in advanced disease. Also, humans get immune to viruses after infection.
And a long history of not becoming wide spread. From TFA "Russell said he and his team had engineered the virus to make it more suitable for cancer therapy." I just assumed the term "suitable" really meant "profitable" but some of the comments indicate it was modified to target the cancer better (how so?). It seems the cost of trials and approvals is too high for a naturally occurring virus, so everyone wants to customize them so they become patentable.
The naturally occurring virus would not treat MM. There is real R&D going on here to make this work as an MM treatment.
From the paper: "Unlike naturally occurring measles, MV-Edm, and hence MV-NIS, targets CD46 as a cell-entry and cell fusion receptor. CD46 is a ubiquitous complement regulatory protein that, fortuitously, is highly expressed on human myeloma cells, making them abnormally susceptible to MV-NIS infection, syncytium formation, and cell killing."
So they tweaked the virus to target CD46 which MM cells express way above normal. The MM cells are therefore significantly more susceptible to being killed by the virus.
I am always happy to see advances in treating cancer. Lost my dad to cancer a few years ago, it would be great if people in the future have a better chance. I know there will always be new diseases, but nipping this one in the bud would be awesome.
I might add there's no such thing as "cancer", cancer is caused by numerous kind of mutations (from various origins, including viral infections) and there's no single bullet against cancer. There are already many good treatments for several types of Cancer but not all, and cancers discovered late have usually bad prognosis no matter what. This being said there are exciting new treatments coming in the 2010s using antibodies instead of regular chemotherapy, which may improve survival for many patients.
I don't know much about cancer, but it seems like a common denominator is that they are all forms of unregulated cell growth.
Doesn't that mean there is such a thing as cancer? Perhaps the final cure would be an augmented immune system that can tunnel to any area of the body and remove these cells. Something like nanobots I guess.
Although I do understand your point, that the several hundred forms of cancer in humans require radically different approaches for curing until nanobots.
From my understanding, the hard part with cancer is that it is not a single "disease" but rather consequences of different root causes. So this is doubtful we will find a single cure for every type of cancer, what we can hope however is to increase our arsenal, but this will likely be a slow improvement during the next century, rather than something as definite as the discovery of penicillin.
From what the article says I think the original virus works by attacking tumors which then explode and spread the virus all around the body. If they use a version of the virus that is safe or that the person is immune to then it would target the cancer and cause it to explode but afterwards be harmless.
That's just the impression I get from the article. I know literally nothing about this do if anyone with actual knowledge can explain properly please do!
(I also know nothing about this stuff.) From the article I gathered that, if the person is immune to this anti-cancer virus, it won't have any chance to do its job before it gets eradicated from the system. Which seems to be a problem: after first attempt this treatment won't work again since one's immune system will definitely recognize the virus (having immune system weakened might do the trick though).
The article also mentions that most people in US are vaccinated—I'm not sure how to read that: vaccinated from this particular virus?
The immune system is so complex that this is difficult to understand. I imagine there is some link to the Abscopal effect, where radiation treatment of one tumor in one part of the body kills the other metastatic tumors.
Don't take it as a very profound observation. I just meant that a cure for cancer from a genetically-engineered variant of the measles virus is the way that all the population in the US ends up turned into zombies in that movie.
Your comment is downvoted, but I had the exact same thought.
What are the long-term risks if we start injecting people with large quantities of a virus to battle another decease? Could that virus evolve into something much worse than cancer?
It's not the injecting large quantities of virus that poses a risk, it's genetically modifying viruses and then exposing people to them that is risky.
I would hope that quarantine procedures around any human made-or-modified virus would be quite strict to avoid something unwanted making it's out of the lab.
Nobody underlined that woman got very high temperature. It could be the reason for the results. Coley's toxins were used century ago for that effect. In fact Sensei Mirai clinick in Japan recently reported remission of ~370 terminal cancer patients using combination of immunotherapy and high dose vitamin C & D, along with termotherapy. Cancer patients usually didnt have temperature long time before diagnosed.
>Two patients in the study received a single intravenous dose of an engineered measles virus (MV-NIS) that is selectively toxic to myeloma plasma cells. Both patients responded, showing reduction of both bone marrow cancer and myeloma protein. One patient, a 49-year-old woman, experienced complete remission of myeloma and has been clear of the disease for over six months.
From the link mentioned in "According the clinic’s statement released Wednesday" line.
I don't see any discussion of the M-count (monoclonal protein) response. My understanding is this is the key measure of myeloma.
It would be really great if this turns out to be a real treatment option because, harsh as it appears from the article, this woman's treatment sounds way easier than the current therapies for myeloma.
Anyone else worried that using virotherapy may result in those virus' building up resistance, similar to what's happening now with antibiotics and superbugs.
Unlike bacteria, cancer isn't spread from person to person, so it's impossible for the treatment of person A's cancer cells to impact the treatment of person B's cancer cells. However the cancer cells within in a single person can become resistant, which is why this treatment is a one time shot.
Resistance to what? There's no particular selective pressure on the virus.
If you mean the cancers becoming resistant, one of the appeals of using viruses in therapeutic settings is they can evolve right alongside their targets, helping mitigate some of those resistance problems.
You've got a good concern, just backwards: the virus is cleared from the patient, but the body becomes immune to the virus. Thus, it can only be used one time, which may limit the therapy's effectiveness.
The paper presents 2 cases, selected because they were the first 2 cases to be tested at maximum viral load. There are additional people in the trial, and they will release full results once they are available.
It included two slides showing before/after blood levels and imaging. They talk about how they modified the virus to emit a tracking signal, and how they modified it to target the cancer cells. Really, really mind blowing and impressive work. I would love a tour of that lab.
These are end-stage patients for whom everything else has stopped working. One of the patients had already undergone several experimental treatments. There is some really exciting research going on for MM (multiple myeloma) treatments, and maybe even cures.
I think this is one example of the free market working well. Typical MM treatment runs about $60k / year, and with recent developments, patients are living 10+ years. Total number of MM patients is increasing both because the disease is becoming more prevalent, but mostly because people are living so much longer with MM. In short, it's a large and growing market. But it's not a cancer you can treat and have it go into remission. You get on treatment, and you stay on it and keep those levels down. The typical treatment is biweekly therapy.
But these OVs are one-time deals. So a single dose treatment is a very interesting alternative. The only problem is, MM is extremely resilient, and the cells are everywhere. It's so hard to eradicate, unless the OV is a cure, it's just another tool in the box to manage MM and extend lives.
Weird, the PDF of the actual paper was freely downloadable a couple hours ago, but now it seems the paywall is up? http://www.sciencedirect.com/science/article/pii/S0025619614...