Reacción a "A therapeutic target has been identified that brings us closer to the goal of preventing brain metastases and avoiding relapses"

It is a very good piece of work that must have required a great deal of effort – as is partly reflected in the number of authors – and has drawn on vast resources to underpin the entire experimental programme. I believe it is worth reporting. I think its preclinical conclusions are relevant, despite potential criticisms that might be levelled at it (though it has already undergone peer review in a rigorous journal). What is not entirely clear to me is its clinical applicability or how to frame it within current therapeutic contexts.

Points I do not like:

1. The distinction between dormant cells and pre-metastatic cells is unclear, and the action of the described pathway and its modification in the former is uncertain. This consideration is important when determining the duration of treatment; whether they lose their quiescence and when they do so will depend on this pathway.
2. Related to this, a biological window for treatment is not the same as an identifiable clinical window.
3. I am not convinced by the post-surgical application; post-surgical radiotherapy to prevent relapse has already been thoroughly proven and is well established. I do not see any immediate utility or application for this finding in this context, despite it being one of the study’s models.
4. We must not forget that systemic treatments carry a risk of toxicity, particularly in situations where the patient may be paucisymptomatic or asymptomatic due to their underlying condition. Furthermore, it remains to be seen whether the treatment is tolerable if it is to be combined with another treatment for the primary tumour; therefore, when and how to prevent such toxicity with this new approach is important and, obviously, given the mechanistic nature of this research, has not been addressed.
5. There is always the risk of model extrapolation (all of which are more or less artefactual), but there is pseudo-validation using a patient sample. Despite this, the finding is worth exploring clinically, provided that the timing and circumstances are clearly defined.
6. It should be made clear in the article that the results come from experimental models and human samples cultured in the laboratory, not from treated patients. False expectations must not be raised among current patients; significant clinical development remains before any potential application. The possibility of preventing metastasis or recurrence remains a clinical hypothesis requiring trials, not a certainty.
7. In this regard, I would avoid exaggerated claims such as that micrometastases can be eliminated or that the drugs have eradicated them. The experiments show a reduction in the metastatic burden, but do not prove complete and lasting eradication. I would use a phrase such as ‘they reduce the viability or progression of micrometastases in experimental models’.