nik_s · HackerTrans

The mitochondria in many cancer cell behave abberantly. For example, in many cases, they can start promoting glycolysis, in process known as the Warburg effect. They're also involved in other processes such as apoptosis and cell migration. I'd hypothesize that these drugs target pathways or processes that are dysregulated in the mitochondria of those cancers.

nik_s

3 年前議論

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.

nik_s

3 年前議論

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.

nik_s

3 年前議論

While I agree with the general sentiment of your message, there are quite a few meta-analyses on pubmed on the long-term safety and efficacy of gastric bypass surgery. They mostly show that while some patients do end up back obese, the majority do improve on many markers of health (weight, diabetes, ...).

Here's an example of a study if you're interested [1]!

[1] https://pubmed.ncbi.nlm.nih.gov/29340676/

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