Alex's Lemonade Stand Foundation squeezes in hope for childhood cancer: an interview with Liz and Jay Scott

Individually, childhood cancers are rare; but, collectively, they impact a huge number of children and their families. Globally, an estimated 400, 000 children and adolescents are diagnosed with cancer every year (Steliarova-Foucher et al. , 2017), and it is the leading cause of death by disease in children after infancy in the USA (Siegel et al. , 2024). The cause of childhood cancer is often elusive, and the most common types are leukaemia, brain tumours, lymphomas and solid tumours, such as neuroblastoma. Efficacy of treatment hinges on early and accurate diagnosis, and each cancer requires a specific treatment regimen. Standard therapies include chemotherapy, surgery and/or radiotherapy, but more tailored, less toxic treatment options are limited. Despite the astounding impact of childhood cancer, it remains underfunded and understudied. Alexandra (Alex) Scott was diagnosed with neuroblastoma just before her first birthday. Despite this devastating diagnosis, in 2000, at the age of 4, she set up a lemonade stand to raise money to find a cure and help other children with cancer. She raised 2000 at her initial lemonade stand, which encouraged people to set up similar stands all over the world. In the years that followed, Alex continued her fundraising activities while battling neuroblastoma, but she sadly passed away in 2004 at the age of 8. Alex and the people she inspired had already raised 1 million to help find a cure for childhood cancer. In 2005, Alex's parents, Liz and Jay Scott, set up Alex's Lemonade Stand Foundation (ALSF; Box 1), and her legacy has continued to grow. ALSF is now the largest independent childhood cancer charity in the USA. Here, Liz and Jay reflect on how their extraordinary daughter has impacted the lives of so many. They also discuss the unique challenges in childhood cancer research and how they maximise their influence to support patients and their families, as well as researchers searching for a cure. Box 1. Alex's Lemonade Stand FoundationAlex's Lemonade Stand Foundation (ALSF) is the largest independent childhood cancer charity in the USA, having funded more than 1500 research projects at nearly 150 institutions across North America and Europe. Since Alex's first lemonade stand, they have raised more than 300 million that goes towards supporting families affected by childhood cancer as well as research. They fund research in two core programmes: Early Career Research and Accelerator Programmes. Both programmes have several grants, ranging from funds for early independent investigators setting up their laboratories to those for more established researchers who are aiming to translate their research to the clinic to improve the care of patients with paediatric cancer. Another area of funding is the Crazy 8 Initiative, where ALSF identified eight prevailing challenges in paediatric cancer that could be solved with innovative and rigorous approaches. ALSF also encourages dissemination of results and cross-disciplinary collaboration to propel innovative research by bringing researchers together at their various research summits and by hosting Childhood Cancer Speaker Series. Although each cancer is rare, these researchers can learn from each other to instil tangible progress. In 2017, ALSF set up The Childhood Cancer Data Lab, which generates tools and databases and provides training to help researchers maximise the potential of big data generated by modern research methods. Another invaluable scientific resource established by ALSF is the Childhood Cancer Repository. This repository collates validated cell lines and patient-derived xenografts from childhood cancers and shares these with scientists to enable fundamental research. Alongside ALSF's extensive funding for research, they provide vital support for the children and families living with cancer. Their Travel For Care Programme helps families pay for travel and accommodation to allow all children to access the treatments they need that may be further afield. As ALSF is built upon lived experience, they recognise the importance of providing opportunities that are not simply for practical reasons. For instance, they offer free professional photography for families to capture precious memories and organise family camps. ALSF also supports siblings of children with cancer through their SuperSibs programme. SuperSibs receive special mailings, online activities and school support, and they can get involved with the Sibling Ambassador Programme, which empowers them to advocate for children and families affected by cancer. Liz: Our foundation is primarily dedicated to funding research to find new cures for all types of childhood cancer. We also support families in many different ways, and we empower people everywhere to get involved and be a part of solving the problems of childhood cancer with us. Jay: Over the years, we've just looked for gaps and tried to fill them. We didn't try to just create something because we felt like it. We tried to create things that there was a need for in the community. So that's how we developed our grant programme. Slowly over time, as we saw needs, we would open up new types of grants and do the same with the services that we provide to families. Liz: As we were raising more money and growing, we recognised that we could put more money in, and we could fill larger gaps. There are still some really large gaps that we think will be pretty expensive to try to fill, so we constantly have a wish list of areas we'd like to fund. As we're raising more money, we're able to put it to use pretty urgently and quickly, because, as parents who have lived through it, we understand that there's a huge sense of urgency every single day to find new cures for kids and to support families. That's where the voice of the parents is louder to me than the voice of the physicians or researchers. It's one thing if you hear it from one person, but if you hear it repeatedly, over and over again, you just can't deny the fact that there are needs that aren't being met. Liz: Well, it's twofold. For the research gaps, we look to the research community to talk to us. We will send out surveys, or we have meetings where they come together. We have a Scientific Advisory Board that we also go to. We combine that with what we hear from families about the challenges they still have across the board, in terms of getting new treatments and the availability and access to the treatments. For our family services, we survey families and social workers in hospitals, but families also come to us every day looking for resources. So, we are tracking those requests to learn about the needs that are coming up again and again in the community of families, which we might be able to solve for them. We also have ambassadors who we meet with quarterly. That's where these needs come up, and they ask if we've thought about funding different areas. I think survivorship is a good example that comes up quite a bit. In this area, families we talked to feel like there are some pretty big gaps, but then when you talk to the physician, sometimes they don't necessarily see those gaps. This is probably because they're maybe not working with the survivors. Those are the problems that I find really interesting, when the community of survivors and parents are saying there are needs that aren't being met, and there seems to be a disconnect. The reality is that there are so many survivors, and there are a lot of needs in the survivor community. That's where the voice of the parents is louder to me than the voice of the physicians or researchers. It's one thing if you hear it from one person, but if you hear it repeatedly, over and over again, you just can't deny the fact that there are needs that aren't being met. Listening to the parents and the survivors, as they get older, is what the best physicians do. I think researchers who aren't seeing patients and are working only in the lab need to take their viewpoint into account to think about the impact their work can have. If you approach your science from that perspective, it might change the way you're making decisions, the aims of your work and how you design your experiments. Liz: We have a pretty collaborative process. When we have an idea and we think there's a need, we will sometimes informally bounce it off researchers in the community. We will also more formally bring it to our Scientific Advisory Board. Usually through these conversations, we all get to the place where we recognise that there is a need and agree upon how we might approach it in a way that is smart, makes good use of the money and could have results. It's not a combative relationship. It's a highly collaborative relationship between us, as we bring ideas from the patient community to our researchers and our scientific advisors, and they help us figure out how we can solve that problem. Of course, you might have ten different scientists, especially physician scientists, and they might have different ideas about what things should be the priority. But generally, we are able to tackle multiple priorities, and we're able to agree on where our bucks can have the biggest bang. You then have fragmented research, where each researcher is interested in a different cancer. We try to bring them together across cancers so that they can learn from each other; even if the exact treatment might not work, a technique or an approach might work from one cancer to the other. Jay: It's a small patient population for each disease. Even if, altogether, there are a lot of patients, there are so many different diseases, and so you have difficulty finding treatments. You then have fragmented research, where each researcher is interested in a different cancer. We try to bring them together across cancers so that they can learn from each other; even if the exact treatment might not work, a technique or an approach might work from one cancer to the other. Liz: Another unique challenge of childhood cancer is that, although everyone agrees that children are incredible, they usually don't have a fully formed voice in their own care. I think there's a balance with parents deciding for children. Depending on the age of the child, I think that can be a challenge for everyone. A huge challenge in general is that children are developing quickly. The treatments that we are using to cure cancer in adults and children were mostly developed for adults. These treatments have pretty detrimental effects on their fast-growing bodies, and those side effects can stay with them for life. Brain tumours are a good example of where there's so much to consider when treating the child and their young developing brain that it makes it extremely challenging compared to treating adults because of those long-term side effects. Liz: When they're invited to go to meetings organised by a foundation to speak, whether it's virtual or in person, really try to show up. It's this whole collaborative circle of allowing foundations to raise more money so that they can continue to pour money into research. And I would think that the researchers get a lot out of it. They get to share their science with a new audience of people, and who doesn't love to talk about what they're dedicating their lives to? If it's a scientific meeting, like our summits where we bring researchers together, they can really learn from others. There are so many opportunities to get involved with a foundation like ours. We have a lot of researchers who do fundraising with us in the month of September for Childhood Cancer Awareness month, and they get their whole lab involved. How empowering is that? So instead of just writing a grant and hoping the money comes in, we're allowing them to have their entire lab, their family members and their friends contribute to the work they're doing. I think that gives them much more ownership and pride in receiving that funding, knowing that they raised it. Jay: The other way they can engage is when they share a success story that's connected to our work. Not only does it get our staff excited about what they're doing, but then we can share the stories with our donors and raise more money, and it just sort of feeds the whole cycle of research funding. So, we work hard to get those stories from researchers. There are some researchers that proactively reach out to us, but not nearly as many as we need. … her story speaks to the successes that are not as final as a cure but show how meaningful it can still be to allow a family and a child to have hope, and to have significantly more time to do the things they want to do in their short lives. Liz: To start with, Alex's life itself was a success story, as far as research goes. No, she wasn't cured, and it wasn't research we necessarily funded, but from the moment we enrolled her in a clinical trial, when we were told she was incurable, she lived 4. 5 more years, and three of those years were very good years. They were some of the best years she had. She was 3 when we were told there was nothing more to be done, and she died at 8. 5. She did so many things in those years, including starting her lemonade stand. So, I think her story speaks to the successes that are not as final as a cure but show how meaningful it can still be to allow a family and a child to have hope, and to have significantly more time to do the things they want to do in their short lives. As far as our funding goes, there's one project out of the Children's Hospital of Philadelphia, with Dr Yael Mossé, who made a discovery about a mutation in some aggressive neuroblastomas, which happens to be the cancer that Alex had. They had treatments that existed for adult cancers with this mutation, and we gave her funding to test these treatments for children in a clinical trial. She had early successes with that trial where children, who were like Alex and were considered incurable, were going into remission very quickly and were staying there. We've met several of those families, so that's one that always stands out to me, because I see now how these children are growing up and living normal lives and doing all the things that I think Alex envisioned when she set up her lemonade stand and wanted to help other kids with cancer. A couple of the moms keep in touch with us, and I get to see what their kids are doing, so that to me shows you the progress. Then, kind of full circle, we learned that Alex's tumour had that mutation as well, so she could have been one of those kids, right? That speaks to how funding research and how work in the lab can actually come through and make a huge difference for children. It can cure kids who would not have been cured 15-20 years ago. Another example is a researcher in Georgia, Dr Ted Johnson, who we gave an Early Career Award to, which, I believe, was his first grant. He was particularly interested in helping children who had relapsed and had hard-to-treat brain tumours. He has been running clinical and families come to who really don't have a lot of other and is able to get them into his one of his various them more time and their In some had children his care for several years who continue to do For that of paediatric brain I think that's really We some of those families, and some of their children have passed but they had more time, and some of them are still doing The they had from their brain tumours have actually with the so their of life is so much they would as a finding this in who was able to offer them something that their child after so many things did not help them to me, is what it's knowing you're making a difference in a it's hard to even put into what that would to those parents and to that we we're always looking for gaps that need to be and we were to fill one of those gaps. in we to our scientific advisors, and are looking to do something with our are some areas that have In our we had thought about big because then it was all in the and it was the When we talked to our scientific advisors, they all up big data so we we were on to That's how we it. A lot of when you start something you go in with the that this going to change something It I think we in 2017, and so it's been 8 years that been doing the work, and it's they do wasn't what we envisioned they would be doing, but they do a lot of things that we in our would have thought they would be doing. of the big things they do is people from childhood cancer on how to use data and how to set up so they can get and then how to the really into data which, from a perspective, makes If we're for this research, we want them to share their so it can help the Our Travel For Care was in to the fact that there are clinical but they're not open as they are in specific It is really to the that only families who could to travel would have access and the for that innovative So, the Travel For Care to at solve some for families who want to go away from their to try an innovative These are always kids who have relapsed or are and don't have other options to If the treatment is they may have to go and for several and there's a short of and they may only have a to So there's and they can't up or even the money in that For a to have to make the that they can't go because they can't the or the or is is That's we the Travel For Care and it's a to for families or to make they have a place to but it's had a huge It's not for these families to have before and they don't involved with a And sometimes the kids are very and they need help getting through the So, there's a lot of and going on For research physicians who are clinical it's really for them to think about these because, at a if they want to patients, they have to think about the of what it would from the patient and the to be able to They need to think about what would be to help them and proactively think about what are If they're being they could think about finding the funds to make that they can help families in the trial. They can also try to with for the work and those things that in It would help It would help the families, which is the whole but it would also help their clinical trial, because get much more If you look at our we want the cure to be more than in the USA. And we want to be able to start out how to raise the in and where in some childhood cancer is probably where the USA was in the In to do that, we need treatments that can be a lot of care and because that's not an in a lot of in the world. That getting away from and out treatments that don't who are in the lab and aren't can find to hear those patient whether it's through their who are maybe paediatric and just and with them or them at the that are going through the on the the that what happens when you're not in an so they have to be to. You don't see the full impact on the kids they get it could be a day could be a after a treatment when they're can't get up, can't get out of can't who are in the lab and aren't can find to hear those patient whether it's through their who are maybe paediatric and just and with them or them at I think and seeing a child who is for their and from the parents about all of the things that go with that, is very and in them the importance of their work. I do think it can the way you think about your research and what the of your research are and what that should which is is this going to help a child who has That's what the research should It's good to learn but you should be things that will get you to that child with cancer is treatments are far from children with cancer are treatments that were for adults. These treatments can have extensive long-term side effects that are particularly in the developing of a child et al. , This the that some survivors of childhood cancer which is often The impact of cancer treatment a life and potential to these side effects is a area of further research. approach is to more as most of these are being developed for getting them for paediatric can be a and process. for childhood cancer are particularly as their cancers are often and there are for these As Liz and Jay these should be to patient which the research while making it more cure for childhood cancer in is and in and where treatment access and care is it can be less than et al. , A core of ALSF is to cure but this is only if innovative treatments can be and in these and This that, upon we need to consider the of and in the of ALSF is to in the scientific as by their of The Childhood Cancer Data 1), and is highly in their funding They maximise the impact of their funding by with patients and their families and patient the USA to research that their Liz and Jay Scott for their to be and for their unique and with us. 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