Contribution to this year’s CLOVES Family Conference

On 07.08.2021, I was given the opportunity to present at this year’s CLOVES Family Conference. This offered me the rare chance to interact directly with PROS (PIK3CA-related overgrowth spectrum) patients and their families, and offer them some of my (limited) knowledge in return for all their support.

Communication of complex science to non-scientists is no easy task but certainly one that we ought to take seriously as researchers. It is our responsibility to ensure that individuals directly or indirectly affected by our work are fully aware of its meaning and, especially, its limitations. It is not merely a sign of professional credibility. It is a sign of respect for the people who 1. inspire our research on a daily basis; 2. contribute to it financially, one way or another.

This belief in humble and honest communication about science, not just with the public but also with other scientists, was largely given to me by my PhD supervisor, Prof Robert Semple, who also deserves most of the credit for my knowledge about PROS and overall research in this area.

The aim of my talk was not only to highlight current research and unanswered questions in PROS, but also what the limitations of available experimental model systems are. I feel rather strongly about the need for such clarification. Nowadays, scientific publications – before and after peer review – are easily accessible, yet it takes a lot of critical thinking and background knowledge to assess the presented findings. Even for a scientist, the sheer number of publications in any given field is often bewildering and impossible to keep up with. Most papers are therefore unlikely to be evaluated beyond titles and abstracts. As I told the patient community, titles, abstracts and even entire publications can often be misleading and inflate the importance of their findings. This is the result of an academic evaluation system where being “first” and “flashy” matters more than being “right” and “rigorous”. To help patients/patient relatives with critical assessment of “PI3K” publications of relevance to PROS, here is a bullet point summary of some of the “tools” I mentioned in yesterday’s presentation:

  1. If it sounds too good to be true, it probably is. Unless claims about treatments and even cures were evaluated as part of a controlled phase 3 clinical trial (and certainly not just in cells or mice), I’d advise a healthy dose of scepticism, with some tentative optimism.
  2. There is no such thing as the perfect model system. All current model systems used in PROS have advantages and disadvantages. My presentation gave some clues as to what those are. Watch out for studies that are only mouse or only 2D cell culture. This information is typically provided in the method’s section. While the conclusions of such studies may be perfectly valid for the mouse or the particular cell type under investigation, extrapolation to the human disease may not be possible. Basically, a mouse is not a human, nor are cells grown in highly artificial culture conditions in the lab. PROS is a case-in-point – it has been very difficult to model the human overgrowth in mouse models. Currently, the best mouse mimic of the disease is not based on a PIK3CA gene that occurs in nature. Cell biology knowledge obtained from this model will therefore warrant replication in a complimentary, “natural” cell model system.
  3. Findings that have been reproduced across a range of different assays, and even better – across different publications/scientific groups, are more trustworthy than those based on a single assay. Granted, this can be difficult for a non-scientist to gauge, but the number of distinct headings in the method section and the diversity of scientific figures may serve as (imperfect) clues.
  4. Be careful not to extrapolate findings from bona fide cancer studies to PROS. While both cancer and PROS may share the same PIK3CA mutations, the contexts are very different.

The point of the above is not to dismiss PROS/PI3K research. Quite the contrary.

There is so much good research in this area, and it would be a shame if it were to be drowned out by less reliable findings. Hopefully, some of the above tips will allow patients and their families to distinguish signal from noise.

The full presentation, including a recording that is slightly longer (35 min) than the original talk, is now openly available via my Open Science Framework presentations site. Feel free to use and abuse as long as the CC-BY license is observed! 🙂