ESMO 2022 | Biological mechanisms of lung cancer initiation and progression

In the original CANTOS trial, canakinumab was tested as a mode of primary prevention for cardiovascular disease. And they also acquired cancer incidence data across a number of solid tumors.

And they saw a really striking dose-dependent reduction in new lung cancer primaries. So that tells you that over the course of the study, exposure to an anti-IL-1β antibody can reduce the risk of new lung cancer primaries. It is a highly significant dose dependent, extraordinary result. It can essentially stop potentially new cancers from forming. It’s a prevention drug.

Now the CANOPY trials are by and large treating established disease, albeit in the adjuvant setting CANOPY-A. Now, I think this tells us, and I think it’s entirely predictable actually, from what we know in the literature, that cancer initiation and cancer maintenance and progression are two very different things. So you’ve got maintenance and progression on the one hand and initiation on the other.

And it may well be that we don’t know, we’re doing these experiments now, that the IL-1β pollution exposure, IL-1β induction transdifferentiation of those cells, there’s a hit and run mechanism and you need to have the anti-IL-1β there to block that mechanism, block that transdifferentiation process from happening. And that first clone from expanding.

And I think it really opens up some opportunities for some fascinating work to really start to tease apart what are the mechanisms of tumor initiation in this sort of inflammatory context. And how do other environmental carcinogens that aren’t mutating DNA feed into similar or parallel inflammatory pathways in other tissues, perhaps promoting expansion of clones with these mutations we see in normal tissue.