Writing this from a squeaky recliner set beside my wife’s bed in the oncology department of a local research hospital.
Three weeks ago she had a radical hysterectomy and partial lymphadenectomy to treat stage IIIc ovarian cancer, and we’re back to try to aid her in her recovery to prepare for chemotherapy. Chemo should start next week, but we are hoping to also participate in a clinical trial for atezolizumab. This is a drug that essentially blocks the cancer cell’s immunosuppressive mechanism (expression of PD-L1) and allows the body’s natural immune response to do work on the disease.
Suddenly inspired to learn more of the nitty gritty around how cancer and the associated therapies work, I’m shocked at how sophisticated the battle is. At least in this case, the unregulated reproduction of cells is just the beginning, and my lay mind can’t grasp how simple mutation is responsible for it. If someone told me cancer was sentient with a will to thrive, I’m now much less inclined to laugh them off.
Therapies that arm our own immune syatem in the fight against this monster really seem like the light at the end of the long, dark tunnel.
Squeeze her hand for a stranger. Every person who has lost someone to cancer, and everyone who has survived it, and all of the people who watched that fight- all of us have her back and stand with her. She's fighting one of the hardest battles put to a person, and she has our respect and awe. I saw my friend at his weakest, and also when he was stronger than anyone I've ever known. It's been years but still, I'm crying. Cancer is personal. Once it touches you, and you see the enemy, you see how everyone is fighting your enemy. I'm grateful to her. We'll be cheering when the bell rings for her- all of us.
Thanks so much for this heartfelt comment. The personification of cancer as an enemy didn't really click with me until my family was directly threatened by it. Reading through the drugs in her chemo cocktail, I come across bevacizumab. A little bit of googling and:
A cancer needs a good blood supply to provide itself
with food and oxygen and to remove waste products. When
it has reached 1 to 2mm across, a tumour needs to grow
its own blood vessels in order to continue to get
bigger.
Some cancer cells make a protein called vascular
endothelial growth factor (VEGF). The VEGF protein
attaches to receptors on cells that line the walls of
blood vessels within the tumour. The cells are called
endothelial cells. *This triggers the blood vessels to
grow so the cancer can then grow.*
Wait...what?!?!
OK, what about this trial...atezzolblablblah.. What's it do?
Programmed cell death protein 1 is a cell surface
receptor that plays an important role in down-
regulating the immune system and promoting self
tolerance by suppressing T cell inflammatory activity.
PD-1 is an immune checkpoint and guards against
autoimmunity through a dual mechanism of promoting
programmed cell death in T-cells in lymph nodes while
simultaneously reducing cell death in regulatory T
cells.
...
PD-L1, the ligand for PD1, is highly expressed in
several cancers *and hence the role of PD1 in cancer
immune evasion is well established*.
Seriously?
This thing isn't just some dumb pathogen floating around that just DoSes your body. It's digging tunnels and cutting phone lines. It has strategy.
If you like reading, I highly recommend Siddhartha Mukherjee's The Emperor of Maladies. It's a catholic overview of the history of cancer research and the modern understanding of cancer as of around 2010. I read it when my Mum was struggling with cancer.
To be fair, most of that strategy is inherited from healthy cell function. As your body grows and cells become further removed from blood supply, they have to send out a demand signal to encourage vascularization of the under supplied region.
Cancer cells simply lack the trigger to stop growing.
Indeed - the theory, that cancer is in fact the primordial default (grow and keep growing) and ordered growth is something that came later springs to mind.
This cancer is being evolutionarily selected for proliferation and resistance to regulation. It is being constantly engineered to destroy.
See also epithelial to mesenchymal (ETM) transition, in which cells lose their anchors and become an entirely different kind of cell so that it can better infiltrate other parts of the body.
It's pernicious and highly specialized because that's why it survives.
And that's why everyone will die of cancer if something else doesn't kill you first.
Are you saying that cancers that are particularly good at their job are more likely to be passed on to the next generation in other people? By what mechanism does a cancer or a cancer mutation spread to the next person?
EDIT: OK I've done some reading about cancer and evolution. Clearly there is an evolutionary process happening inside each person's body that "selects" for cancers that are good at their "job". However even the most successful of those have no hope of passing beyond their host unless they also mutate a transmission mechanism for themselves, which happens much less often (but the Internet tells me it has been known to happen in dogs).
Generally, infectious cancer is a result from a population that either regularly has open wound contact, and or is very closely related genetically.
Given enough time cancer can even start to survive on it's own: https://en.wikipedia.org/wiki/HeLa It's actually become somewhat difficult to avoid cross contaminating samples with this cell line.
There's at least a couple mechanisms. The most obvious is heredity—certain alleles of a particular gene that normally controls growth, or expresses some surface protein, mutate, leaving descendants with a greater risk of cancer. BRCA4, for example, has some variations that all but guarantee breast cancer. Mutation can happen in both somatic (body) cells and in germ-line cells; when it happens in the latter, the mutation can be passed on to offspring.
Oncoviruses are another transmission vector. HPV, or human papillomavirus, is a virus that causes warts (of all kinds) in humans, and also causes several kinds of cancer, including cervical and esophageal cancers.
A third way would be a pretty rare thing in humans, but is thought to be behind some of the canine cancers you mentioned: direct transplantation of cells. The tasmanian devil is on the edge of extinction thanks to a facial cancer they get from each other through this mechanism.
You are right, I was referring to the fact that cancer cells are rewarded as being "more fit" in the body than their neighbors. By gorging themselves on resources and disabling the body's mechanisms for slowing growth, they are rewarded with proliferation.
esp. in combination with studies r intermittent fasts/food in general. Neven Orhel's (fiction) books are also in the line with intermittent extremes / how healthy cells can cope with them and cancer cells can not, which is well in-line with the finish saying(was something like "if sauna doesnt cure you no doctor will" - pls correct me here)
Thanks for this. My beloved aunt was diagnosed with cancer years ago, and has been fighting an awe inspiring battle against it the whole time. She was given bad news last week -- a short and definite time scale. It was hard news for me and more so for her husband, children and grandchildren, but everyone is keeping close in support of her through the hardest part of the fight so far. These battles are so hard to watch, but at the same time just as inspiring. Anyhow, that's the back story, I really just wanted to thank you for posting these words. <3
I understand the need to use some martial metaphor but not everybody is born to see through that lens. The friends I have lost to cancer did not loose a battle. They were strong, they did everything they could, they had a "grandeur d'être" that inspires me until today. But sure, they didn't fail/loose the battle. They were just unfortunate. And their ghosts are still with me.
I don't normally respond to messages like this, but this one touched me. Nearly a decade ago I had to battle a Sarcoma in my leg. It changed the entire course of my life, but has made me stronger as a result. It is an experience I don't wish on anyone, and remembering the impact that it had on my family chokes me up a bit.
I wish the best for you and your loved ones, and genuinely hope your wife beats the shit out of this cancer and I hope she beats it so badly that it never returns. My mother went through ovarian cancer, including the hysterectomies, chemo, and associated therapies. I wish I could tell you it was easy, but I would be lying, it's not.
Incidentally, at least for my mother, the injections she would get shortly after her chemo treatments -- if I remember right these were referred to as "white cell-count booster shots" although I don't remember their actual medical terminology -- these left her feeling far worse than the actual chemotherapy. It most affected her appetite, namely she didn't have one for 3-4 days after getting the injections. We tried everything the doctors and nurses recommended, and a few that the internet recommended [don't do this, but we were desperate], all to no avail. Finally, I talked her into smoking a joint -- and this woman never drank anything other than communion wine or did any drugs in her 55+ years of life before this. Appetite problem solved. It was back in spades, almost like never before. I guess what I'm saying is, if your wife finds herself with the same issues [and I hope she does not] never mind the 'stigma' associated with it -- weed works.
If you haven't already read it, "The Emperor of All Maladies" (B004MPR80E) is a really great book about the history of Cancer and Cancer-like diseases.
The author concludes the autoimmune system is key to beating cancer.
I bought Gene after litening to him on Sam Harris’ podcast (just looked it up, episode 77). Definitely worth a listen, he’s an equally impressive conversationalist. Love him or hate him, Sam’s no slouch either and I left the end of it wishing I had a brain.
I'm curious if there will can ways to use the autoimmune system to fight cancer in people with autoimmune diseases. Knowing someone with RA that has had cancer in the past it really complicates things because stimulating the immune system flares up RA. Often RA treatments involve suppressing the immune system.
as a former scientist in immunotherapy/immunooncology research: we are going to win against cancer.
and very importantly for you and your wife, many of us consider the PD-1 therapies as the biggest battles and biggest victories that we've ever won against cancer. it is extremely difficult to overstate how powerful the anti-PD-1/L1 biologics are.
and it's also extremely hard to overstate how much research scientists in the field live and breathe and toil to harness nature. you have a care staff of perhaps a dozen at the hospital, but just remember that there are tens of thousands of people working day and night to find better therapies and cures.
nature is always throwing us curveballs, and in the words of rich feynman, "she's never gonna let us relax." but we'll figure it out, and win. in the meantime, that clinical trial you mentioned is investigating the true power of our biggest achievement to date.
it isn't ethical to push your wife into the trial, so i'll just say this: if i had serious cancer, i'd find more than one anti-PD-1/L1 trial to try to enroll in simultaneously. that way if i got excluded from one because i didn't meet the criteria, i have a next step in hand without thinking about it any more. if by chance i got into more than one, i'd withdraw from the others (obviously). just my two cents.
My thoughts and prayers to your wife, you, and your families.
My question is: if we boost the immune system, what are the side effects? Is an immune system that's compromised (e.g., loses battle with cancer) indicative of other problems? In other words, in a way, is cancer actually a symptom?
For some reason I wanted to study what cancer and therapies are all about. I reached the same conclusion as yours. The thing is incredibly complex and thus fascinating. After 20 years in IT, I'm seriously considering moving back to university to work on that. All the best for your wife.
My wife and I are about one year ahead of you with the same diagnosis, currently fighting a recurrence. Keep fighting, stay positive. (And yes the science is astounding and rapidly developing.)
Replied earlier, same to you.
----
Sorry to know of your situation. If you want to learn more about a trial in this space (currently enrolling) let me know, I can help.
Thank you brother. Best wishes to you and yours as well, may you come out the other side even stronger in your relationship to each other and your collective resolve to squeeze every drop out of this life we've been graced.
I had the same reaction after hearing about the warburg effect. Basically the synergy of all the bugs that are necessary and maintained by cancerous tissue for it to avoid dying, it's eerie.
I hope your morale is as high as possible, faith and energy are useful to help your loved ones heal in order to endure side effects of treatments. Also it seems immunotherapies are often well supported by patients across the board, so hopefully it will be easier to fight.
I’m sitting in the operating waiting room as I type this while my wife is getting her uterus and right ovary removed, the tumor that consumed the left ovary having been found to be clear cell carcinoma. Her surgeon thinks it was caught at Stage Ia, thank god, but still—fuck cancer so so hard.
If you haven't already, read: Tripping Over the Truth: The Return of the Metabolic Theory of Cancer Illuminates a New and Hopeful Path to a Cure (ISBN: 9781603587303). It is a great review of the history of Cancer. It concludes that the reason for the failed war against cancer stems from a flawed paradigm that categorizes cancer as an exclusively genetic disease and explores therapies born from the emerging metabolic theory of cancer.
Apologies to hear about your wife's cancer. Hope the best of luck fighting to fight.
For adjuvant therapies for cancer, I highly recommend looking into sulforaphane.
Dr. Rhonda Patrick has a tremendous corpus of scientific research and plenty of anecdata on the internet about how it is helpful and has helped others with cancer.
Cancer is a horrible disease. And the current treatments are barbaric. As someone who just finished chemo a year ago, I can't wait for treatments like this to become effective and more mainstream. Best of luck to your wife, and tell her to stay strong!
Sorry for the delay. I don't check HN often. Pls email me on [email protected] with subject line Ovarian Cancer Trial. I can put you in touch with the Professor conducting it.
Echoing the other sentiments here for you and your wife—this is the club nobody wants to join, but we all want to give you a big hug. Its a shitty, scary fight, but some of the therapies coming out now are truly amazing in their potential. My own wife was diagnosed with an immune-mediated cancer a few years ago, and I went pretty deep into the research when that happened. 10 years ago, her diagnosis (melanoma IIIa) had a pretty discouraging prognosis based purely on stats. Today, they're going to have to rewrite a lot of textbooks around those stats.
Hang in there, and don't forget to take care of yourself too. Being in the role of caregiver is fucking exhausting at times. If you're like me, it falls to us to be the shield against well-meaning but poorly informed acquaintances shilling this herbal remedy or that metabolic supplement or this fantastic ketogenic diet backed by the research of some doctor nobody's heard of because Big Pharma... Just nod and smile and say you'll look into that and give them the middle finger in your minds eye. Try and find some support system, whether its a caregivers group or friends who have been through it, or even friends who haven't that you can still vent to. There's a lot coming at you, and more to come. Its ok to take some time for yourself some too.
Best wishes, man—I'll be thinking about your family.
So sorry to hear your story. Cancer just plan old sucks. It has impacted my family and one of my adopted children. My mom had pancreatic cancer (The deadliest of cancers) in 2017 and she is absolutely fine and cancer free a year later. Numbers don't mean anything to the individual and don't look them up is always my recommendation.
As a non-medically trained support member I have gotten pretty good in talking with the doctors about my family members cancers. I help explain them to others in my family and when I sit in the conversations with the doctors I stop them talking to make sure the patient is taking it in and understanding. I have unfortunately worked with many doctors and I have never had a negative experience with one when I stop them and ask the patient do you under stand and have them repeat what they heard. I even did this with my son when he was 8 because it was his body. I would than have a notebook and have them write down their questions throughout the day for when the doctors showed up (Usually around 6 or 7 AM)
I encourage everyone that enters the cancer world, as either a parent, spouse or close friend, to learn everything they can. The more you learn the madder I get at cancer research and specifically about pediatric cancer research. There is a Radio Lab Podcast and it got pretty intense for me to listen but I also understood cancer at a much better concise way after listening to this and specifically how cancer spreads. http://www.radiolab.org/story/91714-devil-tumors/
Three piece of information I always give to everyone:
1) The most important staff member of any doctor or surgeon is the Nurse Practitioner. They are the Master Sargent of that practice. Get their contact information and always make sure they are informed of what is happening.
2) Never assume that the different doctors are communicating, because 90% of the time they don't. Not between the surgeon and oncologist and even residents to other residents. Always ask question to make sure they know what is happening to you. Your the one making sure the different silos are talking.
3) Have two people you can call if you have any concerns. You get a gut feeling you don't ignore it. Doctors miss things all the time and you call that person that you trust. My mom started coughing after surgery and I knew it was serious. Two doctors from the surgeon's team show up and basically don't think it is serious. In the room I calmly said that we both have concerns and think someone else needs to see this. They were figuring out someone else to come to look at her. In the mean time I walked out of the room and called the surgeons nurse practitioner directly and state that I thought my mom's vocal cords were paralyzed, which I already ask the two doctors if they thought that was the issue. We were in the ICU within 10 minutes after that call and we were there for 4 days. My mom's voice came back 2 weeks later, she is a license counselor and her voice is her job. The thing is have a plan on who you can call if you get scared about something.
I can attest from my own interactions that your point number 2 is spot on. My father died of cancer back in 2006, and while I don't attribute his death to this cause directly, miscommunication delayed treatment. Don't expect physicians to call each other, don't expect them to think about you much in their rare off hours. They're human, tired, and busy. Any connection you can make by concentrating on it is one they don't have to make instead.
Wow. Based on the small bit of experience I've had so far it's clear you have been down this road. Thank you so much for the advice, it's getting stowed away for future reference.
If you ever want to contact me my email is in my profile. If I could help in any non-medical questions or advice even just a little bit it would be my pleasure.
We’re 7 years on from stage 1b, similarly drastic surgery (“the works”), eternally grateful that we had kids before. No recurrence but we’ll be watching and waiting forever. My wife is still the youngest person at her doctor’s office by ~20 years so it’s a long goddamn road ahead.
I knew cancer was bad and had a lot of research surrounding it, but I was blown away by the uncertainty for patients and the incredible amount of resources put into solving/treating the disease and supporting the people going through it. After immunization, chemotherapy is probably the most important medical discovery in human history. If immunotherapy can carry us past that, how amazing!
The immunosuppressive therapies are new since we went through treatment and I’m hopeful. If or when we have to fight again, we’ll have new weapons, I’m optimistic.
I hope you find strength, comfort, and support enough to be a support for your wife. Others have gone through it, empathize, and are rooting for you. Fuck cancer.
A different monoclonal antibody treatment successfully treated my grandfather’s lymphoma 10 years ago. It had spread to occupy large portions of his lungs and this treatment was nothing short of miraculous. We watched in awe as the tumors shrunk away.
I don't like to pry, but since my father had rare inoperable non-metastatic brain lymphoma and I have genetic concerns, is he still alive? What is his prognosis? How did he tolerate the treatment? (My apologies if it's too personal to discuss.)
He passed away a few years ago from congestive heart failure at 97. But he enjoyed a good last 10 years cancer free. He tolerated the treatment very well.
Lost my mom 19 years ago to cancerous brain tumors. She was 46 years old (I was 10). Her loss ripped my family apart.
Each family's experience is unique and I can't begin to imagine what it's like to fight the sickness for years.
My heart goes out to the OP's family, and anyone else with an unforgiving disease. I am not a religious man, but I wish your wife the best of luck in her recovery.
I see that authors are from Stanford University. Can someone from the US clarify if this will be in public domain/knowledge, or is it possible some drug company will patent this later on?
If some drug company doesn't pick this up it will fall by the wayside and never make it to market.
On this topic when I was an academic a few years ago I had one of my undergraduate student project groups go through an entire year of Cancer Research (one of the highest ranked cancer journals) from 10 years previously and have them find out what happened to the work published. Rather depressingly the vast majority went nowhere and when my students contacted the PIs to find out why most of the time it was for totally non-scientific reasons like the group lost funding or someone left.
This is just not true. Drug companies will make slight modifications to existing drugs and can get new patents on the new formulations and for new indications. If it works, a drug company can make money off of it even if it's been off-patent for years. See https://en.wikipedia.org/wiki/Lenalidomide vs thalidomide for an example.
For every therapeutic target there are many chemical/biological solutions that can work. If an off-patent compound shows some effect in a pathway, a patentable variant can usually be made.
How can you say this is not true then give all example that require a patent? Yes you can mine drugs that are out of patent and find new uses for it that can be patented. Do you know of one new drug that has come to market in recent years without patent protection?
The difference between (a) an existing, off-patent molecule and a (b) patentable variant of that molecule is somewhat trivial compared to all of the other costs of bringing a drug to market.
But to address your specific question, generics are drugs that come onto the market all of the time without patent protection.
There's plenty of drugs that are made by multiple companies. It might not make sense for a very specific drug which sees low use, but I think it's viable to produce a drug that might be beneficial to virtually anyone even if you don't have exclusivity.
Yes once a drug goes off patent and becomes generic then lots of drug companies will pick it up and start making it, but no new drugs are developed these days without patent protection.
Of course if you wanted to you could make this treatment yourself - it is not that complex.
The issue is who is going to pay for the extensive testing required to get from lab to hospital. That takes years, and lot of organizational skill, and a lot of money. If a drug has gone off-patent, all that is already done, so many companies will be glad to manufacture it. But for new treatments, somebody has to push it through clinical trials, with the (quite substantial) risk that something which looked good in the lab fails to work in larger studies, or has unforeseen side effects.
The approach is in the public domain - in that it could be attempted by anyone else.
According to the paper, these were the two drugs used:
* "CpG SD-101 was provided by Dynavax Technologies"
* "Fc-silent Anti-OX40 (CD134) mAb was purchased from Absolute Antibody"
SD-101 is already in clinical trials. http://www.dynavax.com/our-pipeline/cancer-immunotherapy/sd1...
The anti-OX40 was a laboratory antibody, presumably as this was for a study in mice. However, there are various anti-OX-40 molecules in clinical trials, which could be used.
To get clinical trials going with this approach isn't a matter of patents - it's a matter of one or two companies (depending on ownership of suitable molecules) deciding its something they want to do, and then doing it. My guess is that Dynavax will already be exploring this.
> that authors are from Stanford University. Can someone from the US clarify if this will be in public domain/knowledge
This type of research tends to be publicly funded. However, that doesn't prevent it from being privately patented because of the https://en.wikipedia.org/wiki/Bayh-Dole_Act
One drug is already FDA approved. They have a clinical trial for lymphoma. Stanford may patent many parts of it, the two drug combo.. depends on the novelty and the formulation, how it's delivered. It also depends on how obvious it is in the patent sense. You might find other researchers and companies who optimize the system as well (e.g. fine tune the checkpoint inhibitor). But these drugs are manufactured already. So it seems safe to say that the research will be done and if it works we will see clinical use.
Also by definition a patent is in the pubic domain (for knowledge) and the publication is of course a public disclosure.
Just for clarity, neither drug is FDA approved in the conventional sense (i.e. not approved to be sold). However, both SD-101 and also various anti-OX40 MAbs are in clinical trials.
Also for clarity (and responding to the concerns of the original questioner) it's highly unlikely that this combination will be patented by anyone - this isn't how patents are used in drug development. Anyone with access to the necessary drugs would --in theory-- be free to open a clinical trial to test this approach.
Conflating public domain with public knowledge risks a meaningful error. To patent something requires that you make it publicly knowable, but this knowledge would not be usable by other companies.
well... you can write a patent that is so obfuscated that the public cannot learn from it...
>> well... you can write a patent that is so obfuscated that the public cannot learn from it...
In such case the patent office should reject your patent claim as patent laws usually require that the description of the invention being patented should be understandable to professionals of relevant domain, who should be able to replicate it based solely on that description.
I assune you can patent part of an overall process (certainly that's the case in virtually all software patents), which could be a way to prevent others from replicating your process without explaining the whole thing, no?
We see similar effects when we irradiate tumors with X-rays, called 'abscopal effect'. Sometimes, when you irradiate a tumor, the unirradiated metastases also shrink. It is hypothesized that the immune response is triggered by the irradiation, and there are currently studies being done that try to stimulate the immune system even more.
What I wonder is why this is being discovered only now.
Have you ever seen footage of a white blood cell taking apart a cancer cell? This is worlds closer to unlocking that power than hoping a stray radioactive particle bumps the right lever. Perhaps the need for two separate medicines/agents to make this special cocktail and trigger the perfect immune response has been the elusive part?
Yeah, this is an NK cell triggering an apoptotic (self-destruct) response in a cancer cell. So it's basically sending a kill-signal to the cancer cell, which then kills itself. This doesn't work for all cancers, though. In fact, one hallmark of cancer is unresponsiveness to apoptotic triggers.
Considering that chemotherapy is basically feeding poison to your organism in the hope that cancer cells (which are more active) will ingest it in higher quantity, I'd say that we have a pretty high tolerance threshold in term of side-effects while we are looking for an alternative.
As I understand it, most chemotherapy targets only dividing cells. In adult humans there are relatively few of these: cancer cells (which you want to kill), bone marrow (produces blood cells, so you have to monitor blood cell counts during chemo), and reproductive organs (produce gametes, so you may want to freeze sperm/eggs before chemo).
all things considered, it's probably far more dangerous than chemo in the sense that it could kill you or seriously and permanently injure you with your first dose depending on your phenotype. at least chemo is a slower process.
but immunotherapies don't kill most people, thankfully. there are also many ways that you could assay the patient to see how they might react to immunotherapy, but i dont know whether these are done clinically or not.
Forgive me if this sounds ignorant, but would it not be considered a 'treatment' instead of a 'vaccine' if this is a treatment to the pre-existing condition?
It is indeed a cancer treatment that needs a tumor to work. The authors call their technique "in situ vaccination" because it stimulates antibodies against that specific cancer, which can work throughout the body to destroy metastases.
Cool, thanks for your reply (and those replies below also). I briefly skimmed the article however was sidetracked with work, and admittedly a lot went over my head anyway.
as a former immunooncology scientist i'd say you should be guardedly optimistic. you should be aware that there probably won't be a generalized cancer cure, but i think we'll be starting to tackle a lot of different cancers in the next 2-3 years, just like we have been for the previous 3-5 years. beyond that, who knows.
immunotherapies don't work for 100% of people or 100% of cancers, and some cancers seem to grow resistant to some immunotherapies after multiple rounds of treatment.
there are a lot of limitations and strengths of immunotherapies that we don't even have a clue about yet-- by my totally made up estimation we have about 10% of the puzzle figured out, an additional 30% which we have partial or incorrect understandings of (but at least we realize it and are working to clarify things), and 60% remains unknown unknowns.
but remember: we don't need to understand quantum gravity or have much knowledge of how gravity works whatsoever to make an airplane that defies gravity at our will. it's the same way with immunotherapies, except replace "gravity" with "cancer." we can do an awful lot with what we know.
immunotherapies are incredible-- literally the data is often unbelievable at first glance.
For people outside this field of work like me (a software / cleantech guy), is there a concise spreadsheet to show the state-of-the-art?
i.e. Listing different types of cancers with the most promising immunotherapy treatments for each type, expected confidence and success rates, trials that one can enroll into?
It'd be a good first place to go to whenever we hear of someone who has 'cancer' - that word is so generic that it's hard to figure out what our action item should be.
It's a novel approach, so there is more risk and more reward. I'd guess that it has a 5% chance of making it to market. Most likely, it's ineffective or unsafe (autoimmunity or a more mundane side effect), but it's also possible that that it's effective for many cancers or has very low side effects.
I'm impressed at how precisely and locally targeted the therapy seems to be.
Many of the cancer immunotherapies I've heard about are systemic and risk overengaging a diffuse immune response against multiple tissues. This approach trains in-situ using strong signatures from individual tumors first, before the antigens spread out across the body. Perhaps this localizes the cancer antigen signature better, so antibodies cause less collateral damage?
But CAR-T therapy should do something similar, though re-introduction of the antibodies is systemic (untargeted). Is the administration of this therapy directly into the tumor somehow essential to its specificity?
I've passively followed this field as a layman observer for the past several years. I'd be interested in getting a lot more information on this work.
Generally I view these press releases with a skeptical eye, as the researchers have a need to "talk up" their work in order to keep the funding coming in.
On the other hand, Irving Weissman and the labs at Stanford are well respected and not known for spurious claims - often though, the problem with these therapies isn't so much potency as it is persistence, with recurrences being relatively common longer term (and many therapies simply don't translate from mice to humans well).
I'd be interested in having someone with in-depth knowledge of this field explain how the OX40 receptor work here differs from the CD47 work also being carried out at Stanford (besides being a different target protein), and existing CAR T therapies being tested elsewhere - although certainly this seems very encouraging in any case.
Obviously not as important as the main cause but I wonder if a similar thing could be used to treat warts. I had a wart once and successfully got rid of it by applying a trick I read on the internet which is putting a little square of duct tape on it. Surprisingly it really worked. The Wikipedia page used to list the method with dubious citations and said that one theory for why it worked was that the duct tape stimulated the immune system and caused it to attack the wart when it normally wouldn't.
There may be something to it, as most folk remedies do have an unscientific history of successes, but it definitely doesn't work on all warts or for all people.
As someone very far removed from the medical field, immunotherapy has always seemed to me to be the most logical programme of cancer treatment.
The animal immune system has evolved over hundreds of millions of years to target and destroy pathogens. Why use an indiscriminate chemical treatment to destroy cancer when our body already has a self defense system that operates with pinpoint accuracy, unparalleled target recognition capabilities, and ubiquity throughout the body. All these things make it a terrific candidate to destroy cancer.
> has a self defense system that operates with pinpoint accuracy, unparalleled target recognition capabilities
This isn't always true. You body can start attacking itself if cells start misidentifying one another. This can lead to Lupis, MS, Ruhtomotide Arthritis and various other auto-immune diseases.
The activated T cells completed their training on the target/injected tumor, and then circulated through the body until they found their next target. Trained cancer ninjas.
Another layman's question: As far as I understood, the T-cells recognize cancer cells and kill them because the two agents get injected directly into the cancer site, where the T-cells are surrounded by cancer cells. Doesn't this have a risk of the T-cells misjudging normal body cells as dangerous if they happen to have any of them around, or if the injection happens wherewhere else than the cancer site?
I'm thinking of (1) lower but high enough numbers of normal cells somewhere between the cancer cells, and (2) plain accidents like the needle pushed too far / not far enough.
If I'm understanding the article correctly, it actually can't be used as a strictly preventative measure. It relies on the fact that the subject already has a tumor and that the subject's immune system has made progress in targetting the tumor.
It also seems like that particular cancer mutation is permanently targeted, but yes it’s not like this shot will be given to four year olds as a general prophylactic
Reminded me of this post on reddit[0] about injecting an ethanol gel into tumors (so it has nothing to do with modifying the immune system as in this tactic, just happens to have a similar means of application).
It might seem like noise, but there is progress being made. My cousin's girlfriend takes a pill every day which has basically eliminated her lung cancer for all intents and purposes because it targets the specific mutation which is in the problem in her case.
Relatively new T-Cell therapies "train" the body's own immune system to recognize and delete cancer cells with much fewer negative effects than traditional treatments like radiation or chemotherapy.
Stories like this don't mean an end to cancer, but it's still very good news.
I hate these "XXX found to eliminate cancer in mice" news blurbs. I really want there to be an easy, effective, and inexpensive solution to one of the worst medical conditions imaginable; but they make these kind of announcements 3-4 times a year and 99/100 times they don't pan out because humans are not mice... and medicine is hard.
I'm curious as to why you think that lacking impact is due to dissimilarities between humans and test subjects.
My best guess would have been that a lack of incentives for parties with the power to realize such advancements are overweighing.
We have cured cancer in mice many times. The trick is getting it formulated for humans in ways that are similarly effective and non-lethal. Put another way, signs of efficacy in mice is necessary, but not sufficient, of a human-applicable treatment.
As far as I know we aren’t able to cure cancer in mice. Sure we can cure them of artificial cancers we give them in the lab, but actually curing spontaneous mouse cancer in outbred mouse populations (i.e. something like human cancer) is not something I have ever seen anyone try, let alone succeed.
The article does mention that they also treated a strain of mice that routinely develops tumors in "all ten breasts" and they responded to the therapy too, but not as fully, requiring multiple treatments and not yielding as high a rate of success.
Yes, but I was responding to the OP that claimed we know how to cure cancer in mice, when we have never tried. I suspect that we are actually a lot better at curing real cancer in people than in mice.
Fair point, I was just saying there's still a good chance it'll work (at least if the induced tumors are anything like 'natural' tumors.) Very interested in seeing how this goes, either way.
2) The pathway from first-in-man to approval can be a lot shorter than 10 years for promising drugs or combinations. Pembrolizumab, for example, took roughly four years: https://en.wikipedia.org/wiki/Pembrolizumab#History
Yes there is. The FDA calls it "breakthrough therapy".
For breakthroughs, 10 years before widespread availability would be a maximum. In late stage cancer, especially where options for treatment are few, rollout could be very fast, like 2-5 years.
Not sure, but in the United States there may soon be easier access for any person with a terminal illness to get access to any experimental treatment if they so desire, even treatments that are in early stages with no human trials yet.
Yeah there's a lot of talk about "right to try" laws doing what you have described.
Personally? It had better be an airtight law accounting for the edge cases that could allow certain populations to be taken advantage of. For example, if anyone with a terminal illness can try an experimental drug, could a pharmaceutical company charge for said treatment? Or use the data from trying this treatment on the patient to further their own research?
I guess it just doesn't sit well with me since researchers in the US have had a history of taking advantage of certain populations in furthering progress (Tuskeegee, prison populations, mental institutions).
My gut tells me that if the treatment is given for free (my original comment mentioned I was concerned if the company was charging for said treatments) then there's far less of a problem. However, there's still this incentive for a company to take advantage of this situation. Giving the treatment for free could technically be cheaper than providing the drug in a trial while also paying a participant.
Without being as vague, my main concern is that a pharmaceutical company could find value in business practices that put patients, even those with terminal illnesses, at an unacceptable risk of harm that the patient may not be cognizant of. If the company begins a campaign of fraudulent kickbacks to healthcare professionals we end up with a corrupt system in which we take advantage of patients and their families.
Medicine and medical research goes slowly and cautiously because we wish to protect people. To end this comment, I wish to go back to my statement that if this country goes in the direction of right to try, I sincerely hope lawmakers ensure protection of the patients that could benefit.
I wanted to update you with some new information I remembered. There is already legislation that allows for this, called the Compassionate Use Act. The difference being that the FDA is required to be involved, giving final say on if the doctor and pharmaceutical company can administer the mtreatment to the patient.
there is, but making the jump from mouse to humans with a therapy isn't always successful. sometimes subsequent mouse studies don't pan out, or sometimes the FDA sees something they don't like and you need more research before moving to preclinical development and then phase 1. i'd put it far sooner than 10 years assuming their concept works in humans, though.
Hmmmm, wonder if they could inject the two drugs into a portion of the biopsy sample and re-implant that, assuming the biopsy cells are still viable at the time?
Hmmm, not sure keeping the biopsy cells viable until biopsy results arrive though would be practical.
Both. It's targeted by injecting into one tumour, but many different tumours can be targetted. Once targetted, this tumour is eliminated along with all "copies" in body. If you had breast cancer and colon cancer you would need two injections.
Yes, but it's hard to say yet how much different the therapy process might be in humans. The treatment regimen could differ from mice significantly. (Human tumors may be buried a lot farther away from the surface than in a mouse, and thus, harder to dose accurately with a long needle.)
It's also not clear what toxicities were incurred with this therapy (in mice), which is a significant concern for the approval of any drug in humans.
I hope this will work out for humans as well. Wondering if we can have something for diabetes as well, it seems to be affecting a large portion of the population and growing rapidly.
This kind of reminds me of coley's toxins treatment a little, although a bit different. Really hoping this is successful and can be available in the near term.
This is great. Does it mean we finally have cure for cancer? My granddad died because of that shit, and so did my uncle. Maybe there is still hope for me.
Whenever you hear about amazing breakthroughs in medicine, look to see if it is an animal study. Those usually do not translate into results in humans.
Because what works in animal studies doesn't often work in humans. This is why you hear about a novel cure for cancer in the news every month -- it's always animal studies.
If you want something to get your hopes up, look for stuff undergoing human studies. They're not new(s) -- in fact, it's stuff that is known and has shown promise for years -- but they're more likely to eventually work.
Hey as long as Big Pharma can add their own useless ingredients and nonsense pretty packaging to extort as much money as they can out of patented cancer vaccine flavors, we'll never have to worry about those pesky natural cures that can't be patented and aren't as profitable
I'm happy when solutions for cancer are found. A little less when the way is genetic engineering. From my ignorance I imagine the genetics like a big complex self programming software and the genetic engineering a way to change little variables in a wide enviroment. In other words: Butterlfy effect, you're welcome.
The point of the butterfly effect is that everything you do could be responsible for some massive change in the future. (though the odds are extremely low)
"using this treatment" and "not using this treatment" are about equally likely to cause a butterfly effect.
If applied to an individual person, how does this present any risks of ecological damage? Alternately, does this concentrate control of the food supply into the hands of people who might decide to starve some population out of greed/apathy/prejudice?
Three weeks ago she had a radical hysterectomy and partial lymphadenectomy to treat stage IIIc ovarian cancer, and we’re back to try to aid her in her recovery to prepare for chemotherapy. Chemo should start next week, but we are hoping to also participate in a clinical trial for atezolizumab. This is a drug that essentially blocks the cancer cell’s immunosuppressive mechanism (expression of PD-L1) and allows the body’s natural immune response to do work on the disease.
Suddenly inspired to learn more of the nitty gritty around how cancer and the associated therapies work, I’m shocked at how sophisticated the battle is. At least in this case, the unregulated reproduction of cells is just the beginning, and my lay mind can’t grasp how simple mutation is responsible for it. If someone told me cancer was sentient with a will to thrive, I’m now much less inclined to laugh them off.
Therapies that arm our own immune syatem in the fight against this monster really seem like the light at the end of the long, dark tunnel.