This Taiwan study is bunk, And I don’t say this lightly.
Their human meta-analysis controls arm weren’t other transplant users not taking rapamycin. It was the general population! Considering Sirolimus is used almost exclusively in very sick transplant patients (sirolmus isn’t first line), mostly used concurrently with other cancer-inducing immunosuppressants. They might as well have named it “transplant patients have 2.7 folds increased incidence of cancer compared to the general population”, It’ll be just as valid of a statement.
This is the first time i’ve come across such a disingenuous method of evaluating Sirolimus cancer effect, Other studies at least made attempts to account for confounding factors and at the bare minimum compared sirolimus transplant patients with other transplant patients.
This not only makes me question the author’s competence but also their integrity. Because this misleading method of evaluation is one of the very few ways of presenting sirolimus in a bad light. It’s certainly disingenuous. How did this even pass peer review??
As for mechanism, “ for tumor cell invasion, regulatory T cells, Tregs, are known to play a key role in the metastatic escape of cancer cells…… rapa can enhance the expansion of Tregs…. which may promote the metastasis of mammary cancer in mice”.
There are mountains of studies done on mice, And there is no replicated evidence that rapamycin increases the incidence of any metastasis or cancers (apart from hematological malignancies in very extreme high doses). It’s mostly the exact opposite.
It’s also been extensively tested in human transplant patients, And there is still no evidence that sirolimus specifically increases the incidence of any cancer or metastasis. If it increases the risk of metastasis we would’ve seen indications of this by now from multiple studies, However, many of them show the exact opposite, And in worst-case scenarios show no benefit. Certainly not increased risk.
Everolimus is even FDA-approved because it has shown an increased survival rate when used for the treatment of her2 negative metastatic breast cancer
Some mice studies, but not all, lean toward cancer prevention
The vast majority show cancer prevention and slowing of cancer progression. Not just some.
- A Human meta-analysis shows no real cancer protection.
The correct framing is that Sirolimus when used in transplant patient with other immunosuppressants does not appear to confer cancer protection. Putting the big limiations of this meta-analysis aside one can speculate why. It could be that sirolimus protects against cancer by keeping immune cells young and when they’re nuked by another drug, Sirolimus can’t do much to help stop cancer. It could also be that sirolimus anti-proliferative effect is only useful when the immune is intact, And its anti-cancer effect is not impactful when the immune system is severly compromised.
@Senolytic did a great breakdown of this meta-analysis and its limitations. Interestingly most of the RCTs in this meta-analysis that used Sirolimus alone (not in combination with other immunosuppressants) demonstrated lower trends of cancers, Which is consistent with mice studies. Although they did not hit statistical significance, They barely missed it, And there can be many reasons why. (which was not the case when sirolumus was used with other immunosuppressants)
- The most public and prominent promoter of rapamycin for longevity and disease prevention,most notably cancer prevention, himself comes down with a very aggressive cancer after years of rapamycin usage.
This is not even a valid point. It has no place in any scientific or objective discussion. This is no different than someone questioning the benefit of exercise for cancer prevention because their fitness instructor got cancer, Or the benefit of aspirin because their cardiologist got an MI.
These decisions should be guided exclusively by high quality evidence-based experiments. There are no large-scale human rapamycin trials, And this is enough for many not to pursue it. However, appeal to emotions has no place in any decisions.
