I have a friend who about 15 years ago was told he was going to die from melanoma in about a year.

Within that first year he was put on a trial that added another 2 or so years to his life. Then during that time another experimental treatment was created and tested on him and that gave him another couple of years. A decade and a half later here we are, he still has cancer but his family (wife and two kids) has got to keep him around a while longer.

He’s been “patient one” on a number of studies, some have helped him extend his life expectancy, others have done nothing. Sometimes he has the mental and physical energy to start a trial and other times he does not.

The cancer has never gone away, and there have been so many moments of false hope that I’m never really sure where he sits mentally anymore (he really doesn’t want to talk about cancer when we’re together and I don’t think anyone can blame him) but I know he’s grateful for the chance to add more time onto his life when the experimental treatments are available.

The thing about trials is that there's a reasonable chance the patient ends up in the control/placebo group, which is something to think about when signing up for miracle. It could help explain some of the "done nothing" studies in your friend's journey.

A good friend of mine signed up for a trial as an alternative treatment for her aggressive breast cancer, everyone's hopes went up (trials tend to have that effect on people) but "nothing happened". She passed away 6 months after the trial started without knowing if a placebo was used. It's painful anecdata, but the few people I know that got into cancer studies as an alternative to their regular treatment, none ever had the study knowingly influence their outcome. Yet, in every case, the study was the one-hundred-percent animic lifeboat to grab on to.

Participating in a trial is about helping science just as, or more than, it is about helping yourself.

Yeah he always took some pride in being that early patient in a study.

As an aside, I’ll have to be careful here because I think I might be confusing some of the trials he was a part of with actual treatments he received. It’s been a big mix of throwing a lot of different things at the wall.

Yeah my friend has been doing that for about half as long. It still sucks. Some of the modern, immune-based therapies don't make your hair fall out, but they still can wreck your digestive tract, thyroid, and adrenals(in my friend's case, permanently). There are surgeries as well, and getting slowly hacked up as they chase tumor after tumor isn't fun.

Still though, it's a better time to have cancer than ever I suppose.

I’m sorry your friend is in a similar position.

There was one treatment that they were going to trial my friend on that would give him another expected extension but basically make his digestive tract stop working so he’d be pooping out of a tube into a bag the rest of his life but he declined, said it just wasn’t worth it.

There have been a couple times that’s been the call he’s made and I appreciate why.

Good luck to your friend - sometimes it is not worth it, but the chances he has been taking and the suffering he has been going through in those trials where it is worth it is hopefully helping others in the future with the same disease.

Cancer sucks; why it is so hard for us to beat is so frustrating. need more research focused on this.

He is both fortunate and unfortunate. Must have a very difficult fifteen years.

Is that study a randomized controlled study? Was your friend in the control group or in the experimental group? What was the difference of the outcome in both groups?

It's very rare that everyone in the control group dies and everyone in the experimental group survives. Usually the result is mixed.

The problem is that medical doctors sometime make bad guess about how many years the person will survive. That's one of the reason to have a control group, so the error in the guess compensate.

For anyone reading, the control group for cancer trials is the best current treatment, there’s no placebo control.

Yep, standard of care is used in control groups. Also, there are trials in which people are moved from the control arm to the experimental treatment upon increase in tumor size, which allows participants to get a chance to actually trial the drug.

Vince DeVita said it was the main strategy in the 60s. Extend enough to find a new idea. Today things are standardized but if you fall out of the solution, you're given morphine and a bed. Which I find dreadful. Your friend life is a, pardon my french, interesting story.. because he managed to jump above deadlines but I can understand how spiritually damaging it is to always take your fate in your own hand every few years.

Good luck to him

The new immunotherapies should be tried if he hasn't done any yet.

Assuming you have found a drug that is safe and binds the target in the intended way (which itself can take years), you then have to manufacture it according to GMP standards. That takes at least a year and $1 million. Next, you have to run toxicity and pharmacokinetics (how the drug is absorbed and distributed in the body) in two different animal models. That takes 6-12 months and $1-2 million. Then you apply for permission to start phase I trials, and wait for the green light.

One reason RNA drugs are so exciting is that their manufacture is simple and can be standardized, cutting the GMP manufacturing step to a few weeks instead of a year or more. Small-molecule drugs are ”bespoke” in that each needs its own, different, manufacturing process. In contrast, all RNA molecules are essentially chemically identical, differing only in the ordering of the nucleotides.

Need to make a drug out of the small molecule inhibitor. There is a medicinal chemistry process that takes quite a while (several years at times) to get to something you can actually give to people.

Then there is safety testing in animals. Then regulatory approval. Then starting the phase I trial. The trial might take a year or more. Then you need to show the drug works compared to some standard treatment, which in a phase 3 trial in breast cancer takes 3 years and many hundreds of patients at least. Longer if you want to show it prolongs overall survival. Then the drug needs to be approved.

There is also the matter of funding but there is a lot of money for early stage biotechs at the moment.

In my (unpopular) opinion trials for people with incurable cancer are quite predatory. You are supposed to participate to help science, not yourself. But in reality many people desperately cling to anything that gives them hope.

The article seems to suggest that they only just found a compound which will interfere with the gene's action. So up until now, there was nothing to test.

The 2014 result only showed that gene editing before birth might prevent cancers.

From the article:

"yet it doesn’t seem to be important for normal development"

Gene space is huge. My cancer is cured, but now I'm dying of mange. So that's why that mouse kept licking itself. Big ask for someone else. They have trouble getting blood thinners, statins and beta blockers right. And there's no genetics there. It's stuff people ate out in the woods for hundreds of thousands of years.

> There are so many people close to dying in cancer finding volunteers for a Phase 1 test should be easy

I take the opposite approach. These people have few days left. It's a time to make things nice. It can get much worse quick. Cancer, which can be managed, is nowhere near as bad as it can get.

Disease tends to hit all at once. It's really just dying. Cancer, strokes, heart attacks and infections all tend to gang up at once. The trial will kill these people no doubt. If you have a ticket out of the hospital, take it! Don't squander it trying to wash mud.

Also the patient pays a lot for clinical trials. Hundreds of thousands of dollars.

You seem to be getting downvoted. Not sure why.

I've had someone in the family who got cancer. It was basically how you said it would be. They lived their life to the fullest, not thinking about the untreatable cancer. Do whatever is fun and makes you happy.

At some point it got bad. No more living your life. There were bad moment. There were better moments. There were worse moments. I only saw it from afar until the very end. The last bit must have been hell for the closest family. It really is just dying. Slowly. Painfully. And all society and doctors try to do is to prolong the suffering.

I'm being unfair to some people. I do know the palliative care team did their best. All volunteer doctors. Power to them.

Agreed (except the part about the patient paying for clinical trials). After I got diagnosed with metastatic prostate cancer last year I was asked to participate in a immunotherapy trial. I declined as a wasn't about to spend the next two years (that could very well be my last) going to the hospital every three weeks to be poked and prodded.

Wait what? Trails aren't free to participants? That alone is going to majorly bias the results.

Here take this medicine, we are fairly confident it won't kill you. Here is your $100k bill. Oh? Can't afford that? No trial for you!

Trials are absolutely free for the participants. Insurance won’t pay for non-FDA approved treatments and it’s illegal to charge for them anyway.

Ancillary routine FDA approved testing that accompanies the trials may be billed to insurance in some cases? I don’t know about that. But a trial for a novel cancer treatment will be free, if not even include an honorarium of some kind to defray costs to the patient for participating.

Generally patients don't pay extra for clinical trials, although it's complicated. Their insurance usually pays for patient care costs, routine costs you'd have regardless of the trial. The trial usually pays for research costs, tests and stuff specifically due to the research.

https://www.mskcc.org/cancer-care/clinical-trials/frequently...

Acquiring endless regulatory approvals.

I don't mind that it takes a little proof to convince regulatory boards to approve medicines for Phase I trials, but these days Phase I trials are fairly quick to get (assuming you can sell the doctors and patients on it).

My guess for the delay is production process and delivery mechanisms. There are delivery mechanisms where the combinatory effects lead to some serious toxicity.

Plus, how long do mice live for? I'm sure they are still taking down observations and collecting data. The article submission may be to help with funding.

I wonder how much of our regulation around medicine is wasteful, vs regulation that came about in response to some sort of malfeasance.

Most of it is probably both.

I worked in medical devices, and that is correct. Much of the work I did in the QA dept would not have improved the product or safety, but some of it clearly did. Can't say for medicines, as they had a different set of regs from devices.

It is both. The last time we had very free experimentation (read: disregard for human life and suffering) we got the Nazis, the Tuskegee Syphilis Study, MKUltra, etc.. So institutions swung strongly in the opposite direction (the visible ones, at least), giving us Institutional Review Boards and such. The balance is impossible to get right either way, hence the need for Right to Try and so on.