In one sense, it’s a revolutionary step forward. In another, it’s what we’ve always been doing. As surely as children find strange things in their imaginations, our cells get rid of proteins we don’t need.
They have to. Almost all the things our cells do involve making proteins. They can’t let those proteins hang around when their jobs are finished. That would be like everyone in your house deciding not to clean up after eating. Within a week, the kitchen’s mouldy and cluttered – and there’s nothing left to eat off.
Cells aren’t too different. Apart from in size, that is – and you need to be even more careful about cleaning up in small spaces. You might even want to find ways of using the same things for different tasks. Once they’re finished with proteins, our cells degrade them into the tiny pieces they need to make new ones.
It’s recycling. All our cells are doing it all the time.
“It’s an inherent process,” explains Eilers. “The same way our bodies are always making things, we continuously degrade proteins that we don’t need.”
We definitely don’t need cancer driving proteins, but they’re so unusual they don’t attract the attention of the waste-disposal system. Degrader drugs just point them out, and then the system does its work.
Better drugs with fewer side effects
In the first place, this means degraders can affect previously undruggable targets like MYCN oncoproteins. They should also work better against the messages sent by ALK. Whereas inhibitor drugs leave dangerous proteins intact (which means they can break loose and find a new way to deliver their messages), degrader drugs get rid of them completely.
What’s more, because degraders specifically target the features of oncoproteins that make them stand out from healthy proteins, they should cause far fewer side effects.
“This is an opportunity to target precisely the drivers of these childhood cancers,” explains Mossé. “And, as these proteins are expressed mostly just in the tumour and not in healthy tissues, we have a chance to go after them without causing children harm.”
Everyone’s futures
Liz understands that potential as well as anyone. It’s why, as well as running the ALSF, she and her husband Jay decided to join KOODAC as patient advocates.
“I don’t usually love being a patient advocate because it takes so much time,” she says. “Every hour is so important when you’re fundraising, but I couldn’t resist being part of this. Now we’re crossing borders and bringing more organisations together to solve these problems. That’s exactly what we need.”
Cancer touches all of us. It’s not something we can face alone.
“I think Yaël said this story could be told through Alex because Alex stands for so much. But she’s just one child. It’s every child: that’s what this means to me.
“It’s about this community – and it’s more than an oncologist in Philadelphia and a biochemist in Germany, as well. The kids are part of the community, and the parents are part of the community.
“Alex started this with a simple idea, but the magical thing is how people come together, and the work that’s being done to make the idea so much bigger.”
Every child has big ideas. They might save lives, or they might just make you smile.
We’re working so more children can see where their ideas lead.
Tim
