Anti-tumor activity of all-trans retinoic acid in gastric-cancer | Hacker News Reader

Anti-tumor activity of all-trans retinoic acid in gastric-cancer

pubmed.ncbi.nlm.nih.gov

47 pointsbirriel22 comments

I work in drug discovery (including in oncological indications), so it's always great to see new research with early, promising results!

To summarize the paper: some gastric cancer models are sensitive to all-trans retinoic acid (ATRA). ATRA is an active metabolite of vitamin A, and is already used clinically to treat some hematological cancers. The researchers tested the compound at several concentrations on a number of gastric cancer cell lines, where they show moderate to significant reductions in growth (from 30% to 60% reduction). Next, they tested ATRA on xenografted tumor cells on immuno-compromised mice, where they also show a reduction in tumor size. They hypothesize that ATRA exerts its effects through immuno-modulation.

Firstly, very cool, and congrats to the authors - I definitely see first evidence of the potential of ATRA to treat gastric cancer.

While I might have misunderstood some parts, I do think there are some elements that warrant precautions here: 1. we can see that some of the untreated mice also show reduction in tumor size, albeit less significant, meaning there could be issues with the cells or protocol, 2. I find it hard to conclude anything about ATRA exerting its effect through the immune system in a study of cell models and immuno-compromised mice.

Nevertheless, given the frankly poor prognosis of gastric cancer (many patients in early stages of the disease now get their stomach removed, and more often than not, these tumors metastize aggressively), and the well known safety profile of ATRA, I think the study is very welcome, and should warrant further investigation. Given the hypothesized mechanism of action, I think testing on humanized mice, using more and more distinct patient-derived cells would bring convincing proof to move ATRA forward to clinical trials.

Small PSA:

I’ve got stage 4 colon cancer- I see these sorts of articles passed to me from family members.

While encouraging that these discoveries are being made it’s not necessarily something that you can take to the doctor and get started with. The following needs to happen:

1- it applies to your cancer/genetics/geneticdefects 2- it’s in a stage that you can be part of testing in human trials which means usually a specialist cancer hospital. (As a side note I recommend MD Anderson as a treatment hospital. They treat me very well and advocate well with insurance fights. And if you have cancer, live in the US you will fight with you insurer) 3- Is it even ready?? Usually no. It’s just the first paper written about it and others need to reproduce the results. Then about 10 other lucky miracles happen and human trials can start. 4- don’t be afraid to go back and forth with your doctor.

I’m currently doing maintenance chemotherapy but some areas flared up and they wanted to add another chemo drug. There were 2 options and we discussed and went with the option I tolerated better.

I do HIGHLY recommend that you establish a rapport with your doctor so that you can discuss treatment options freely. The way it works at MDACC and I’m sure very similar to other cancer hospitals. Is they do all the typing and dna sequences up front. It helps them diagnose the cancer and prognosis etc. and then that lives in your chart. Typical treatment is to use traditional known chemo treatments and if they are not effective they start adding the trials that match your dna/cancer type.

Very long winded way to say unless someone in your life asks you to send these sorts of things it’s kind of like getting a lottery ticket for 10 years from now.

Stage IV CRC as well. Agreed, for the vast majority, it is still cytotoxic chemotherapy. I used to follow these innovations hoping to bring it up with my onc, but rarely do any of them work better than standard of care in vivo.

I hope you're handling maintenance chemo okay. Tumor DNA can change over time, so get a biopsy at some point to see if you qualify for other treatments.

The maintenance was pretty easy tbh. 5FU for 15 minutes (bollus) once a week.

Great point about tumor dna. It does change and the “usual” treatments become less effective. That’s when the experimental drugs are usually brought in to the treatment plan.

I am living a pretty normal life for 4 of 7 days. And honestly I’m grateful it’s only 3 days that I’m less productive or just kind of tired/ spaced out.

Another PSA- start your start up before health gets in the way. Health really is wealth and having time with energy and a clear mind is in shorter supply once health issues arise. But also balance work and life. Ok no more PSAs today :)

Health really is the only wealth, amen to that. Ah, my 5FU was a 2 day pump affair that left me in a totally nauseous haze; I do not miss that at all. 4 out of 7 days is great.

I hope you are able to get to even more tolerable therapies in the future!

> And if you have cancer, live in the US you will fight with you insurer

Why the fuck is this a thing? You pay for insurance. They should be on the hook. That's the arrangement.

Can you be denied treatments if the insurer won't pay and you can't afford it?

Pretty simple: it cuts into their profits. Your health is secondary to that.

I don’t know why it is a thing. But it is. Can give you a great example.

I was diagnosed in 2020. Went to a local oncologist who said (initially) I was stage 1. We caught it early. Then they do the colon resection and I wake up to the news that I’m stage 3c. I went through a 6 month treatment which knocked it back using the standard treatment (FOLFOX) and it was undetectable. Cut to 6 months later and it was back with a vengeance.

My oncologist ordered genetic testing right at the same time I decided to go to MD Anderson. The first thing that they wanted to do was the same genetic test. Great we say. My old oncologist ordered it.

My insurance BCBS declined to pay because my old oncologist ordered it and not the current one at MDACC. We / the hospital wrote 3 protest letters and they denied the claim meaning we had to pay 5k for the test. After dealing with insurance and the testing company we negotiated a lower price but be prepared to do so.

If you can’t afford it you are sometimes able to get payment plans. And there are endowments for situations where money is tight or no insurance. None of it is fun that’s for sure. Insurance companies are not your friend.

> Can you be denied treatments if the insurer won't pay and you can't afford it?

Yes, or you get treated but go broke. Medical bankruptcy is very common in the United States but unheard of almost anywhere else, despite those countries having better health outcomes. At some point paying three times as much on average is going to swamp everything else.

There’s been tons written about this over the years but some recent articles I read:

https://www.propublica.org/article/priority-health-michigan-...

https://www.propublica.org/article/blue-cross-proton-therapy...

That's the problem in the US, people are fighting so much for remote problems that were fed to them by politicians trying to be elected that they don't see the real problems they face. If all that energy was directed at changing what can make or break an individual or even in that case a family, people would have much better lifes. And the same goes with food quality and availability, it is absolutely disastrous on health and yet most of the areas in the US don't have easy access to non shitty food but have all the junk food they want.

It is important to note that all-trans retinoic acid is standard therapy for some types of myeloid leukemias, most notably acute promyelocytic leukemia (APL) and it is also routinely used for treatment of neuroblastoma (a pediatric solid tumor). However, in both cases the cancers show an arrest in differentiation, which ATRA helps overcoming, so I am quite skeptical it will be clinically effective in tumors that develop from fully differentiated cells (like gastric cancer does).

https://www.lls.org/treatment-acute-promyelocytic-leukemia

Also known as tretinoin, the acne treatment.

Can anyone simplify this?

They are trying to turn a natural metabolite of vitamin A into a drug that they can sell to cancer patients because the natural metabolize vitamin A inhibit cancer growth.

It would be better to eat more organ meats.

It's more complicated than this. The conversion of vitamin A (carotenoids) to ATRA is highly regulated by various enzymes, and giving ATRA directly will bypass the enzymes and result in much higher doses than would normally be achieved.

ATRA he found an organ meats like the liver.

But when not eat healthier in the meantime?

Listen, it’s better to prevent cancer than to have to take some special metabolite drug of vitamin A for a gazillion dollars to cure it, isn’t it?

Hmm... I'm not sure that follows. The ACE-inhibitor drugs like lisinopril (and several others ending in -pril) are front-line drugs for treating high blood pressure. I take lisinopril myself, as do other friends and family members.

The ACE-inhibitors are modifications of a substance found in the venom of Bothrops jararaca, a South American pit viper. Scientists observed that when a prey animal is bitten by one of these snakes it experiences a sudden and profound drop in blood pressure (ideally to zero, from the snake's point of view).

You could argue that allowing yourself to be bitten by one of these snakes would somehow be more "natural" than taking a pill, but myself, I'm going to stick with the pill. :-)

While perhaps not as dramatic, vitamin A is also quite toxic in large amounts. Some of the early polar explorers came to grief from eating sled dog livers or other animal livers.

You’re making a false equivalent.

There are many other ways to control high blood pressure as well, and one of those includes diet.

> You’re making a false equivalent.

Not at all.

You: taking Vitamin A in a pill is unnatural. You should get it naturally, by eating organ meat (at the potential cost of getting sick from Vitamin A overdose, which is something that actually happens).

Me: taking an ACE inhibitor in a pill is unnatural. You should get it naturally, by allowing a snake to bite you (at the potential cost of dying from the snake bite).

There's no "false equivalent" here. The statements are exactly analogous.

I think this is a very cynical take. Patients with gastric cancer are often in a dire situation: many of them have had their stomach removed and have generally significant difficulties with digestion, which makes consuming specific foods very difficult. The therapeutically effective doses of ATRA are also high compared to what you'd get from foods, meaning that injections are nearly the only solution for these patients. Finally, naturally derived compounds generally have the weakest patents, so if anything, we should thank these researchers for looking into the therapeutic potential of these drugs. I can assure you that few pharmaceutical companies would research this, as the commercial incentives are really weak to do so.

I’m talking about prevention not cures.

All-trans retinoic acid (ATRA) is a form of Vitamin A which is used to treat one particular type of leukemia. This group tested it against some gastric cancer cells. Not sure why it's on the front page of HN.

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