So there’s been a great deal of interest in new agents that can be added into the curative intent treatment paradigm for patients with head and neck cancers. Regrettably, in the last five years, we’ve seen a number of attempts to add immune checkpoint blockade to standard of care chemoradiation, they have failed. So we have to think freshly as to how to exploit these opportunities to combine new drugs with standard of care chemoradiation to improve outcomes...
So there’s been a great deal of interest in new agents that can be added into the curative intent treatment paradigm for patients with head and neck cancers. Regrettably, in the last five years, we’ve seen a number of attempts to add immune checkpoint blockade to standard of care chemoradiation, they have failed. So we have to think freshly as to how to exploit these opportunities to combine new drugs with standard of care chemoradiation to improve outcomes. Now, one of the things that we are learning is that the way in which a cancer cell dies may be relevant to how the body responds to it and in particular how the immune system sees that event. So we are now beginning to frame a way of thinking about how to treat the disease whereby we see the death of the cell not as the end point of what we’re trying to achieve, but actually the jumping off point for subsequent treatment that we try to then trigger. So in that regard, rather than simply killing a cell through an apoptotic event, maybe we can reprogram the form of cell death into another type of cell death. So there are a range of different modalities whereby cells can die in a more immunologically visible way. And these include events such as necroptosis, ferroptosis, pyroptosis. And all of these forms of cell death will lead to the release of inflammatory mediators into the extracellular environment and can potentially activate inflammatory responses within the tumor itself. So there are drug discovery programs based around targets such as RIPK1 for necroptosis, which looks particularly attractive. Other targets which can potentially modulate ferroptosis and pyroptosis. And I think we will see drug discovery programs coming to the fore in those areas. So it’s an area of great excitement.
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