I've commented on this around here before. You read lots of junk about cancer "cures" in the popular press. They are almost always in mice or something and I or someone else with a similar background always feels compelled to weigh in and remind folks that it's a long way from curing lab rats to curing people.
This however, is the real deal. It's quite remarkable and there's likely more stories like this for other diseases on the way.
I went to a gene therapy session this fall at the American Society of Human Genetics conference in Boston and was blown away by some of the success people are having. I quipped to colleagues that I felt like I was in a science fiction movie. The most remarkable one was where they used an approach similar to the one here to cure a fatal metabolic disorder (relaying this from memory, so some of my recollection may be off). Kids with the disorder have a busted enzyme that causes slow degeneration of neurons. They don't live past 6 or 7 if I recall. The team showed how modifying a certain kind of stem cell found in the body normally to have the correct copy of the enzyme cured several patients. The corrected cells naturally move to the brain where they differentiate into glial cells and produce the correct copy of the enzyme. It turns out that because the neurons in the brain are starved for this enzyme, they express receptors that allow them to take it up from the environment. So the repaired glial cells supply enzyme to the entire brain (i.e. it's not necessary to modify every neuron in the brain to have a correct copy of the enzyme). They can completely cure kids with this approach. All of their muscular and neurological tests are 100% normal.
They had videos of these kids running around and playing just as if nothing was wrong. In one case, a younger brother lived but his older sister (who was too old when the therapy came out) had died. It was hard not to get choked up looking at their smiling, happy faces as they ran around, thinking that if this therapy hadn't existed, they would be in a nearly vegetative state.
Gene therapy had a rough start with the early setbacks, but I'm getting the sense that the tide is rapidly turing.
I'm not an expert, just an interested layperson, but from what I read, I am starting to wonder whether cancer cures might be more basic than we realize, we're just not looking at the right things.
The example that keeps coming to mind is HPV - it can cause cervical cancer etc. And, since there is an immunization for HPV, the disease is preventable, and to the extent it is the "only" cause of certain cancers, would also prevent those cancers.
So is HPV the "only" virus which causes cancer? Seems unlikely. I just don't know how much research is focused on bacterial or viral origins. Maybe it is not glamorous or mysterious enough to justify funding.
The 2005 nobel in physiology went to Barry Marshal for discovering that stomach ulcers, long a mystery, were caused by Helicobacter pylori bacteria. And in fairness to history, he wasn't even the first person to discover it, just the most recent person in western society.
I used to work in anti-infectives research and if you talked to virologists long enough they would all insist that huge numbers of human ailments were caused by as yet undiscovered viruses. I admit that I'm a bit biased toward this myself. But I also have worked with people who are mitochondrial experts and they are convinced that huge amounts of disease are caused by mitochondrial defects. Lots of microbiologists think undiscovered bacteria are to blame.
The bottom line is that they are likely all correct. There is a staggeringly large amount of biology that we just don't know anything about. The complexity of it all is almost fractal. Just when we think we've got our heads around something, we peel another layer off the onion to reveal an entire landscape of which we were previously unaware. The best example of this is the recent findings in epigenetics. Before Darwin, Lamarck argued that acquired characteristics could be passed on to offspring. This was widely discredited. I learned about how it was patently false in high school. Now, we are finding that DNA methylation patterns (which work sort of like commenting out blocks of your DNA code) are modified and passed on to offspring. In some studies, if a mother is stressed, her offspring have stress response genes turned on by default at birth. In another, if there is starvation, the animal has starvation survival genes enabled at birth. It's quite remarkable and it means that in addition to our DNA which is fairly static, we have this parallel inheritance pattern that can be shaped and molded by the environment and passed to our offspring. The old "nature vs nurture" debate gets a whole lot more confusing (and might even be the wrong question entirely) with that in play.
Viruses are only one potential cause of cancer, and there are several known tumorigenic viruses (HPV, adenovirus, EBV, polyomavirus, etc.). There are still researchers that believe that all remaining cancers are caused by yet undiscovered viruses (the "viral hypothesis"), but these researchers are becoming scarce.
It seems more likely that cancer can also be a disease of aging and degeneration. As we get older, things break. Cellular division is liable to be one of those things. There are identified mutations that dramatically predispose people to cancer, because one of the genes controlling cellular division is already broken (the "Knudson hypothesis").
Some researchers do prefer to use the viral cancers as a model for studying the others, because they luckily have a singularly identifiable cause, and therefore seem more likely to point to the causative mutations behind cancer as a general process. This is the premise for a paper that I helped author: http://www.nature.com/nature/journal/v487/n7408/full/nature1...
Nitpick: in the same vein, not all gastric ulcers are caused by H. pylori. Another common cause is chronic NSAID (e.g. ibuprofen) use.
Your link lost me at the first sentence. But the word "phenotype" reminded me of this 11 minute Khan Academy video. Maybe I'm just repeating the same thing. But I thought Sal's video was worth sharing and easily digestible.
For whatever reason, Breast Cancer prefers to metastasize bone (which is a phenotype). Something as simple as giving cured Breast Cancer victims a calcium supplement can significantly reduce remission. Phenotypes >= Genotypes?
Prevention of cancer is not a cure, and it would not prevent all types of cancer. Cancer can appear anywhere in the body without any significant "cause". Regular safe sun radiation can be enough to alter certain DNA part during regular cell divide and immune cells might fail to spot the cell and it can start reproducing. Unlike infectious diseases, cancer is the result of evolution within body, it is fundamental to every multicell organism.
"Finally, that one of the simplest of diseases managed to utterly confound us for so long, at the cost of millions of lives, even after we had stumbled across an unequivocal cure. It makes you wonder how many incurable ailments of the modern world - depression, autism, hypertension, obesity - will turn out to have equally simple solutions, once we are able to see them in the correct light. What will we be slapping our foreheads about sixty years from now, wondering how we missed something so obvious?"
To be fair to him (and co-discoverer/recipient Robin Warren), it's one thing to notice something; another thing to prove it. And he proved it by drinking the bacteria himself.
[ An interesting criticism of modern science is that by demanding proof, it rejects all truths that are not proven. ]
Cancer may be similar, though I suspect it's a syndrome i.e. not a single cause and cure; but many causes, and therefore many treatments.
I think one effect is that "cancer" is actually a very broad umbrella term. Different cancers have very different causes, characteristics and prognoses.
Indeed you are right. For much of the time people have thought that at least you could classify cancers by the tissues where they present themselves (e.g. colon cancer, breast cancer, prostate cancer, etc...). But more research is showing that this may actually not be so simple. At the molecular level, it's possible for two cancers from different tissues to be identical from a mechanistic standpoint. There is a lot of re-thinking going on in the oncology community about how cancers are classified and treated as a result.
Yeah. It then gets even more complex when a cancer spreads as another secondary cancer to a different part of the body. You suddenly get the specialists scratching their heads about who guides the treatment.
I knew someone a while ago (who recovered) who had a secondary brain tumor. His doctors basically admitted -- they had no idea what effect the cocktail of drugs he was taking would do. The drugs were complex in themselves, let alone in (probably unique) combination.
I think one very accessible innovation in medicine is genetics and drugs. Even just (relatively) simple genetic-drug effect matching could yield some big improvements.
This is already beginning to happen- melanoma patients are screened for V600E mutations to determine if they can receive new treatments, as with breast cancer and tamoxifen or her petit although this happens with immunohistoxhemistry rather than sequencing.
The V600E mutation also appears in some other cancers (bowel, from memory) so occasionally used there too
The BRAF V600E gene mutation occurs in about 55% of melanomas. The fact that there are targeted therapies to address that mutation is hopeful. Unfortunately, the first generation BRAF-inhibitors showed quick and early promise (shrinking many patients' tumors tremendously), these effects only last 12 to 18 months (at most), as new melanoma cells develop in the body resistant to the BRAF-inhibitation. So, now trials are combining BRAF-inhibitors with MEK-inhibitors to attack the path that melanoma cells often take to circumvent the BRAF-inhibitation. This approach is showing further progress.
It's a bit like whack-a-mole. Unfortunately, it takes time and money to find the best treatment paths.
Fortunately, more progress has made in the fight against melanoma in the last five years than the previous twenty. As a 2.5 year melanoma survivor (Stage IV in Summer 2012), I'm appreciative of this fact each and every day.
Your body is constantly surveilling for cancer cells and eliminating them; in doing so, it selects for cells that can evade the immune system. By the time you have large tumors, the cells are already quite good and evading the immune system, at which point your adaptive immunity system can't help you. These scientists are trying to do first-order engineering on the immune cells to make them more effective.
We've seen this before in science, with antibiotics. A few major, early wins followed by the long silence of failure, due to second-order adaptation by cells.
"We've seen this before in science, with antibiotics. A few major, early wins followed by the long silence of failure, due to second-order adaptation by cells."
But the key difference is that cancer does not pass from person to person, unlike bacteria. All cancer cells die before or with the patient, they don't stick around to "remember" how to defeat the hack.
If we do get some major, early wins, they are likely to be very reproducible, indefinitely.
I do not intend this as a contradiction but merely a tangential tidbit: Devil facial tumor disease [0] is an example of an actual, transmissible cancer in mammals, showing that it is at least possible.
We also know that cancer can be spread / caused by virus, from one person to another (eg HPV, and there are probably others waiting to be discovered).
And we know that you can intentionally force the formation of tumors / cancer through introduction. We do this in mice as a regular course of study now.
I suspect that over the coming decades, we're going to find cancer is a far more communicable disease than previously thought.
Tumor cells form populations; within the person, there are many generations of expansion and adaptation. Within that time, they definitely "remember" how to defeat the hack.
Yes, but other people are unaffected by that one person. That doesn't mean 100 percent chance of cure, but the chance remains the same for every person.
you're just pointing out a minor difference in my analogy. in cancer, the "population" is the tumor cells in a single human's body, while with bacteria, the "population" includes invading cells that infect multiple people and carry resistance between them. In both cases, the dividing cells propagate their inherited traits that allow them to evade the immune system or treatment.
When you treat a person with a cancer drug, the cancer tumor population evolves (selection and natural variation), when you treat a population with an antibiotic, the bacterial population evolves. That was the point of my analogy.
The analogy is valid, but the difference is not minor.
With infectious disease, if there are ten possible mutations to make the pathogen resistant to treatment, each with a 1% chance of happening within the course of the disease in one patient, then pretty soon all mutations would be present in most of the whole pathogen population on Earth, because of natural selection.
With non-infectious diseases such as cancer, in the same scenario, there would be about a 10% chance of the cancer cells developing one or more of the mutations in each patient, period. A tragedy for those 10% of patients, but a cure for the other 90%.
you're missing the point. cancer is internally infectious. Primary tumors don't even really kill people that much- patients almost always die from metastases. These metastases typically are more resistant.
Please read the entire book "Molecular Biology of Cancer". I'm just explaining small parts of it.
I guess the question then becomes: can the cancer cell population in a single patient evolve fast enough to evade the newly improved immune system, before it gets killed off completely?
It seems unlikely. The genetic diversity was already created. Even when people report "we cannot detect any cancer cells in this person's body, so they're cured", they aren't saying there are no repositories in the body that harbor some resistant cells, whcih will then go walk up the exponential growth curves every aggressive tumor always does.
Almost every thing we do is passed on to and alters the next generation we give birth to, even if only in a very subtle way.
My question would be, why wouldn't cancer continue to evolve with our immune systems? We're not abolishing the process that leads to cancer, or making cancer impossible. This therapy kills it after it comes into existence. What would prevent a modified immune system from being passed on, and what would prevent an evolution on the kind of cancer that said immune system is susceptible to? That is, why wouldn't the next generation of cancer become that much more challenging to fight, requiring constantly evolving the therapy?
Not asking to be pro or con, but genuinely curious about this.
> What would prevent a modified immune system from being passed on
The fact that modifying your immune system doesn't automatically modify the part of your DNA that encodes how to create an immune system. Children don't inherit your experiences, they just inherit your DNA. (For the same reason, cutting your leg off doesn't cause your offspring to have a missing leg.)
How exactly is cancer adaptive anyway? Think about how natural selection works: genes that are better at surviving and propagating themselves survive and propagate themselves. Bacteria evolve because they're an independent genome that infests other organisms but cancer is just a failure mode of biology.
Cancer is adaptative in the same way. Tumors are populations of cells with variation (forget the part where your teachers said tumors are composed of clones, that's garbage). When you apply a selection, a small number of the cancer cells survive. Usually there are several different subpopulations. Then they grow, you end up with tumors that are mixed populations of different subtypes. Then the cells start growing again.
Saying cancer is just a failure mode of biology isn't given cancer enough credit. It's more like cancer is a side effect of complex organisms, which is nearly impossible to eliminate, without also eliminating a number of highly advantageous features of cells.
But they're not transmitted from host to host so the only way it would be passed from patient to patient is if a patient himself had genes for resistant cancer and that somehow made him more likely to spread his genome.
>We've seen this before in science, with antibiotics. A few major, early wins followed by the long silence of failure, due to second-order adaptation by cells.
I would hardly call antibiotics a "long silence of failure" - they are still pretty goddamn effective, even if they aren't quite as effective as they once were.
While anti-retroviral therapy for HIV/AID does not cure the disease, it has transformed a diagnosis that would otherwise have been a death sentence into a manageable illness.
If a "first order" treatment for cancer only extends lives by a few years or even decades, how is that not progress?
Does anyone know if this can be applied to other cancers too? I think they only mentioned leukemia, but they seemed to imply that it would be applicable to other cancers. But would the therapy have to be for each cancer or broadly for all cancers? And I am guessing they would have to choose between this and chemo, since I think chemo hurts your immune system. And that would be a difficult choice, no?
The reason this works is that there happens to be a protein on the outside of leukemias that allows you to uniquely target only the cancerous cells, leaving everything else alone. Provided a similar molecular signature could be found in other cancers, it might be possible to do this elsewhere.
I've read about this before. I'm excited and cautiously optimistic about it moving forward. One hopes that it can save other people in the future. Even some is better than 0. Personalised immunotherapy is cool :)
My mom had cancer surgery at Sloane Kettering in NYC. After surgery, which removed most of the cancer, she was put on a treatment regimen that involves a certain type of medicine (which she'll be on for the rest of her life.)
Because she matched a gene, she's able to take a medicine called Tarceva. In essence, this medicine makes her lung cancer a chronic illness -- it's present, but doesn't spread or metastasize. It's a similar strategy to the one now employed with people who are HIV positive.
If I had a promising new drug, I'd want someone with years of experience in getting a drug approved helping me out and the billions in capital to get it done wouldn't hurt either (which of course is available because Novartis sold a number of profitable drugs).
The professor who came up with this science is going to get a cut of that, as will the university.
Zinc finger nucleases are effectively obsolete; CRISPR systems do the same thing, but you don't have to develop custom proteins- just supply the approprately synthesized complementary DNA.
My wife was diagnosed in September with stage 1 breast cancer. She has triple negative breast cancer which is the most aggressive kind to get. She is on week 6 of a 16 week Chemotherapy regimen. Then she has 8 weeks of radiation.
Insurance has already spent over 100k on her lumpectomy and chemo drugs and doctor appointments since September.
Every week when we go to her oncologist office, the waiting room is always full with patients we have never seen before. More than half of them are new patients filling out their new patient paperwork. And they are getting younger and younger in age. We have seen teenagers in his office with breast cancer.
There is just too much money (doctors, surgery, drugs) to be made from treating this disease. What are all of these trained oncologist surgeons/doctors going to do if cancer gets cured? What are the drug companies that make these expensive chemo drugs going to do if cancer gets cured?
There is no way they are going to cure this horrible disease. There is no money to be made in the cure.
I think people who make these arguments drastically underestimate the challenges faced in coming up with a single cure-all for cancer.
That said, I am very sorry to hear about your wife's condition and I hope that she comes out of it fine. That must be an extremely difficult situation and I'm not sure if I were in your situation I wouldn't have a similar opinion.
> There is no way they are going to cure this horrible disease. There is no money to be made in the cure.
The "they" who treat cancer are not the same "they" who will cure it. It's like saying auto mechanic design cars to fail. Auto mechanics don't design cars at all, and have nothing to do with that.
You sound like you have a depression, which is completely understandable, since you can not in any way help your wife. There are good reasons why every cancer can not be completely and effectively cured in every case. But it will be cured, it's just a matter of time.
I'm so sorry you and your wife are going through this. It's an awful experience, hopefully it'll be over soon and you two can move on with your lives.
Something to keep in mind is that cancer isn't just one disease, it's a huge cluster of diseases with similar presentations. I survived testicular cancer this year, which happens to be one of a group of cancers that is almost completely curable. Thirty years ago it was not the same story, with a 90% five year mortality. Now it's 95% five year survival. That said, two close family members passed away this year from other types of cancer, one kidney and another colorectal.
I guess my point is that each type of cancer potentially requires a different cure, and some are easier nuts to crack than others. Leukemia has a promising future as one of those curable cancers.
I don't feel that way. I see all the money that is being made from the ongoing treatment of Cancer. Drugs, surgery, scans, follow up appointments, radiation, and then the cycle repeats when the cancer returns or comes out of remission.
That makes no sense at all. You do realize that developing a cure for a disease can be even more profitable than just trying to treat it, right?
Look at the new HCV treatments. Previously, you'd have to take two drugs for most of your life. Three different companies have developed treatments that cure HCV in 90%+ of the patients with only 12 weeks of treatment.
I vaguely recall this being posted before a few months back, but in a long-form journalism writeup in a local Philly paper...I can't recall exactly where but I remember it was well written.
If/when the cure makes it through the final tests to the market, the sad thing is that they are probably going to rip off everyone who needs it, no matter what are the real costs.
The "real" costs of making ordinary drugs are small in terms of manufacturing. It is very inexpensive to synthesize the chemicals that make up most drugs. You're paying for the R&D of the drug as well as all the ones that failed along the way. In the days when software used to be sold in cardboard boxes and came on CD's, nobody was making the argument that someone like Microsoft should charge a few dollars since CD's and cardboard are cheap.
All that said, in this specific case, the therapy is enormously complex, time consuming, and expensive. It's not a simple chemical compound that can be manufactured in bulk. Furthermore, it has to be tailor-made in a lab under highly controlled conditions for each individual receiving the treatment. As a result, it is likely to be extremely costly when it finally makes it out of the experimental phase.
"It is very inexpensive to synthesize the chemicals that make up most drugs"
Can I ask a stupid q? How exactly inexpensive is it? Thinking in line of 3d printing, how possible could it be to get the chemicals needed, and the machines needed to mix them appropriately, to make a known drug? Ie, how possible would be to "download a pill"? The recipe, and you make it yourself at home?
Yes, but that's still sky high price for most of the world. And if they put price order of magnitude less, won't it bring around order of magnitude more people who can afford it and they money outcome will be pretty much the same? Look at pharma companies: https://en.wikipedia.org/wiki/List_of_pharmaceutical_compani...
They are very profitable, maybe we should make them less profitable and more effective widespread-wise?
I don't think you understood his point. Even though this drug costs $84K, it's still cheaper than current treatments that include prolonged hospitalization and liver transplants.
It's sort of like people complaining that Lipitor costs $5K/yr. The fact it prevents a number of heart attacks, means that it's actually a cost saving treatment.
This is exactly right. 84K is a drop in the bucket for cancer treatment. I have been going through cancer since 2008, and GVHD since my stimcell in 2011. I had no insurance when I was diagnosed at age 23 at top physical condition of my life. The financial aid program at North Side Hospital in Atlanta and Medicaid system of the US of A has kept me alive. But I know I probably have over 3 million in debt in my name alone. 84k would be nice.
You know those "greedy insurance companies" that the US is struggling to wrangle with complicated legislation and broken website markets? They only make 3% margin.
> You know those "greedy insurance companies" that the US is struggling to wrangle with complicated legislation and broken website markets? They only make 3% margin.
Of course, that's after paying out executive salaries, including bonuses for "cost cutting".
Executive compensation is subject to market forces. You can't waive a magic wand and cut executive salaries without losing upper management talent and running the company into the ground.
You're missing the point entirely. Executive salaries can be a magic wand for insurance companies to go "look how low our margins are!" by funneling what would've been profits into the pockets of their already highly-paid execs.
I mean by all ways. Abolishing or shortening patents maybe part of it sure. There's a lot of people/scientists who want to work and help people. We just need more effective ways to let them do so.
I know, I live in a country with socialized medical system. It doesn't matter. Socialized system means everybody pay collective check to those pharma companies. The issue I was talking about is more effective way of inventing and distributing drugs.
The point is, it's a cost improvement over the current situation.
I'm a single-payer advocate. I too think market-based healthcare fails society. Within the context of it, though, this isn't as outrageous as the plain dollar amount seems.
- Many people don't spend every penny they have. They spend every penny they can get out of their health plan. That's not a "market failure" by any means agreed?
- If they must pay out of pocket, and they have no kids, then why not? If they do have kids, then that seems a bit selfish to me. Maybe the right thing to do is save the money and buy cheap painkillers.
Not every sad story is Oliver Twist. And the argument that single-payer health-care will be cheaper is a crap-shoot at best. The countries that do it well do many things well. I don't see dramatic savings from US single-payer education. Or from single-payer defense spending.
Even in single payer systems, bankruptcy is often the result of medical issues. You have to remember that many conditions prevent you from working, so even if your medical bills are paid, you still can't afford your daily expense.
Interestingly, it turns out that research commissioned by the Canadian government shows that 15% of people over the age of 55 who declare bankruptcy cite a medical problem as the primary reason. Medical bankruptcies can, as I've been saying for a while, be driven by something other than the lack of free government provided medical care.
True but irrelevant, since there is a huge difference between being bankrupted by the medical system itself, and bankrupted because you can't afford not to work (which can happen for many other reasons and is a separate problem to guard oneself against).
I don't think it's irrelevant at all. People throw out the statistic that X% of Americans go bankrupt because of medical problems inferring it's because we don't have single-payer healthcare.
The statistic about Canada backs up the idea that isn't true.
This however, is the real deal. It's quite remarkable and there's likely more stories like this for other diseases on the way.
I went to a gene therapy session this fall at the American Society of Human Genetics conference in Boston and was blown away by some of the success people are having. I quipped to colleagues that I felt like I was in a science fiction movie. The most remarkable one was where they used an approach similar to the one here to cure a fatal metabolic disorder (relaying this from memory, so some of my recollection may be off). Kids with the disorder have a busted enzyme that causes slow degeneration of neurons. They don't live past 6 or 7 if I recall. The team showed how modifying a certain kind of stem cell found in the body normally to have the correct copy of the enzyme cured several patients. The corrected cells naturally move to the brain where they differentiate into glial cells and produce the correct copy of the enzyme. It turns out that because the neurons in the brain are starved for this enzyme, they express receptors that allow them to take it up from the environment. So the repaired glial cells supply enzyme to the entire brain (i.e. it's not necessary to modify every neuron in the brain to have a correct copy of the enzyme). They can completely cure kids with this approach. All of their muscular and neurological tests are 100% normal.
They had videos of these kids running around and playing just as if nothing was wrong. In one case, a younger brother lived but his older sister (who was too old when the therapy came out) had died. It was hard not to get choked up looking at their smiling, happy faces as they ran around, thinking that if this therapy hadn't existed, they would be in a nearly vegetative state.
Gene therapy had a rough start with the early setbacks, but I'm getting the sense that the tide is rapidly turing.