CaPPtain's Blog: John Burn, February 2024

The end is in sight.

Fewer than 25 of our 1879 CaPP3 recruits are now awaiting their final 60 month follow up visit.   We need to have all of the 60-month visits completed with the data added to MACRO by 30^th June 2024.  This includes those participants who withdrew but agreed to follow up and bloods, so that we can begin the study analysis.  Needless to say, the results are eagerly awaited and will be pivotal in our efforts in the UK to complete the repurposing of aspirin as a cancer preventive in Lynch syndrome.

The first two years of the intervention were blinded to capture a reliable record of adverse events in the three dosage groups.  These data are with Tim Bishop and Faye Elliott, the study statisticians, for processing and we hope to have this analysis ready for the summer.

We have been working for five years with colleagues in London, Boston and Italy as part of the AsCaP programme funded by Cancer Research UK to explore the way aspirin works.  An exciting piece of research has recently been published by our Italian partners.  They have bred a mouse which has a gene change making it prone to bowel polyps and has the gene for COX1 out of action.  Aspirin blocks COX1 in platelets, the tiny blood cells which block small leaks.  It also blocks COX2 which is active in inflammation.  For a long time, we have assumed the main anti-cancer effect is based on blocking COX2.  In the mouse model, stopping COX1 from working suppressed polyp formation.  This supports the idea that activated platelets expressing COX1 might then trigger the COX2 effect.  This is important because platelets are blocked by small doses of aspirin, and it would explain why studies involving very low dose aspirin still show a reduced rate of cancer.  If this is the main effect of aspirin, then we would expect the similar levels of protection against cancer in all three groups taking part in CaPP3.  On the other hand, if a direct effect on inflammation is important, then there should be more protection with the bigger doses.

We are now planning more research into these questions while we await the final data from CaPP3. 

In June I will attend the inaugural Cancer Prevention Conference in Boston sponsored by Cancer Research UK, the American Cancer Society and the US National Cancer Institute.  I am a co-chair of the conference alongside Tim Rebbeck from Harvard and Thea Tlsty from University of California.  The plan is that the three-day conference will bring together the research community around cancer prevention and stimulate new ideas and studies.  It will be in the UK in 2025 and continue to alternate thereafter.  Needless to say, we will be keen to talk about the CaPP3 results next year!

John Burn
February 2024