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Dr. Brenda Weigel is on the front lines of developing new drugs for pediatric cancer. We caught up with her to learn about the latest developments in precision medicine — and how philanthropy makes a difference in her work. Dr. Brenda Weigel is one of the world’s leading experts in developing drugs for childhood cancer. She directs the Division of Pediatric Hematology/Oncology at the University of Minnesota Medical School. She has also led the Developmental Therapeutics Committee at the Children’s Oncology Group (COG) for over a decade.
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At COG, Dr. Weigel collaborates with other researchers to identify which new drugs have the biggest potential to help children with cancer, and helps guide those drugs into the COG pediatric research pipeline. We caught up with her to learn about the latest developments in precision medicine, what inspires her research and how philanthropy makes a difference for the children and families who participate in research.
Q: What is the Developmental Therapeutics Committee and how does it advance new pediatric cancer treatments?
COG is home to 12 disease committees that focus on specific types of cancer. At COG, the Developmental Therapeutics Committee’s job is to evaluate new drugs that are in the pharmaceutical companies’ pipelines. When our committee determines a drug is promising, we lead small, early-phase trials to evaluate whether that therapy is safe, whether children can tolerate it and what the pediatric dose should be. Those early trials usually include kids with different types of cancer.
From there, we take our results to the 12 disease committees that focus on specific types of cancer and we help those committees decide which new drugs have the most potential for their patients. Those disease committees build on our work by designing clinical trials that test the drug in more children. Those larger trials can help us take the next step and determine whether the drug can be effective.
Q: How does precision medicine fit into developmental therapeutics research and what are we learning about its potential?
Generally speaking, the idea behind precision medicine is that we can identify specific targets on cancer cells and then use drugs to hit those targets and slow down or stop the cancer. The vision is to be able to screen a child’s cancer cells, find specific targets on those cells, and then match them with drugs that aim at those targets. Ideally, this would be more precise than chemotherapy, with fewer side effects.
A study called Pediatric MATCH – led by Dr. Will Parsons from Baylor – has taught us some really important things about this. The study screened kids across the country whose solid tumors aren’t responding to treatments to see if we could identify specific mutations on their cancer cells. And it was successful at that – it found that a high proportion of those children have mutations that could theoretically be treated with targeted drugs. But there are challenges.
There aren’t yet many drugs that match those targets. Those targets are only present in a very, very small percentage of children with cancer – so even if you do have a drug, it will only be usable in a really small number of patients. And even when you have a single drug that hits the right target, our studies show it doesn’t usually make a big difference in terms of actually stopping the cancer.
There are some exceptions. COG studies led by Dr. Ted Laetsch of Children’s Hospital of Philadelphia are finding that a drug called larotrectinib can be remarkably effective against cancers driven by a very specific genetic change. But that’s very unusual, which suggests that we need to investigate combination strategies.
This could mean combining a targeted drug with other things – maybe a chemotherapy or another novel drug or an immunotherapy. We’re doing research on this, to find out if there are specific therapy combinations that work against particular types of tumors.
Q: What are some of the biggest challenges your committee faces?
Most cancer drugs are developed for adults and then we find ways to apply them to kids. That’s harder than it might sound. You have to do a lot of preclinical research to see if, for instance, a drug’s dose needs to be different in children versus adults.
Fortunately, there was important legislation passed a few years ago – the RACE for Children Act – that better prioritizes pediatric research. When a new drug could be relevant to pediatric cancer, the act requires that pharmaceutical companies also study it in kids. This means that there is now real recognition that this pediatric research is important, and it caused pharmaceutical companies to develop teams that focus specifically on pediatric oncology.
Dr. Steve Dubois from Dana Farber showed that, before the RACE for Children Act, it took around seven years between the time a company started developing a drug for adults and the time it started applying that drug to kids. That process is getting faster but still takes longer than we want it to. That’s one reason why the Developmental Therapeutics Committee has regular meetings with pharmaceutical companies, so we can understand which drugs are in their pipeline and get started on trials as quickly as possible.
Q: What is the Developmental Therapeutics Committee and how does it advance new pediatric cancer treatments?
COG is home to 12 disease committees that focus on specific types of cancer. At COG, the Developmental Therapeutics Committee’s job is to evaluate new drugs that are in the pharmaceutical companies’ pipelines. When our committee determines a drug is promising, we lead small, early-phase trials to evaluate whether that therapy is safe, whether children can tolerate it and what the pediatric dose should be. Those early trials usually include kids with different types of cancer.
From there, we take our results to the 12 disease committees that focus on specific types of cancer and we help those committees decide which new drugs have the most potential for their patients. Those disease committees build on our work by designing clinical trials that test the drug in more children. Those larger trials can help us take the next step and determine whether the drug can be effective.
Q: How does precision medicine fit into developmental therapeutics research and what are we learning about its potential?
Generally speaking, the idea behind precision medicine is that we can identify specific targets on cancer cells and then use drugs to hit those targets and slow down or stop the cancer. The vision is to be able to screen a child’s cancer cells, find specific targets on those cells, and then match them with drugs that aim at those targets. Ideally, this would be more precise than chemotherapy, with fewer side effects.
A study called Pediatric MATCH – led by Dr. Will Parsons from Baylor – has taught us some really important things about this. The study screened kids across the country whose solid tumors aren’t responding to treatments to see if we could identify specific mutations on their cancer cells. And it was successful at that – it found that a high proportion of those children have mutations that could theoretically be treated with targeted drugs. But there are challenges.
There aren’t yet many drugs that match those targets. Those targets are only present in a very, very small percentage of children with cancer – so even if you do have a drug, it will only be usable in a really small number of patients. And even when you have a single drug that hits the right target, our studies show it doesn’t usually make a big difference in terms of actually stopping the cancer.
There are some exceptions. COG studies led by Dr. Ted Laetsch of Children’s Hospital of Philadelphia are finding that a drug called larotrectinib can be remarkably effective against cancers driven by a very specific genetic change. But that’s very unusual, which suggests that we need to investigate combination strategies.
This could mean combining a targeted drug with other things – maybe a chemotherapy or another novel drug or an immunotherapy. We’re doing research on this, to find out if there are specific therapy combinations that work against particular types of tumors.
Q: What are some of the biggest challenges your committee faces?
Most cancer drugs are developed for adults and then we find ways to apply them to kids. That’s harder than it might sound. You have to do a lot of preclinical research to see if, for instance, a drug’s dose needs to be different in children versus adults.
Fortunately, there was important legislation passed a few years ago – the RACE for Children Act – that better prioritizes pediatric research. When a new drug could be relevant to pediatric cancer, the act requires that pharmaceutical companies also study it in kids. This means that there is now real recognition that this pediatric research is important, and it caused pharmaceutical companies to develop teams that focus specifically on pediatric oncology.
Dr. Steve Dubois from Dana Farber showed that, before the RACE for Children Act, it took around seven years between the time a company started developing a drug for adults and the time it started applying that drug to kids. That process is getting faster but still takes longer than we want it to. That’s one reason why the Developmental Therapeutics Committee has regular meetings with pharmaceutical companies, so we can understand which drugs are in their pipeline and get started on trials as quickly as possible.
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Q: What’s one of your committee’s biggest recent successes?
Several years ago, we started an early-phase study of a drug called cabozantinib, led by Dr. Srivandana Akshintala at the National Cancer Institute (NCI). At the time, there was clear evidence that this drug could help patients with certain forms of thyroid cancer. Our trial included patients with different types of cancer and we found something we didn’t expect. The drug improved progression-free survival in some children with osteosarcoma – their tumors either shrank or stopped growing. We had never seen that kind of result for osteosarcoma. So our committee took that information to the osteosarcoma committee and they used it to develop a very large, randomized, up-front Phase 3 trial. The trial includes children with metastatic and non-metastatic cancer. All of the participants get chemotherapy, and some get cabozantinib as part of their initial therapy. This will help us to determine if cabozantinib can potentially be effective against osteosarcoma right from the start. It's a really great example of how we took a drug that had never been given to children, did the initial study to figure out the dosing and tolerability, and came out finding a potential for real benefit in osteosarcoma. It’s the first time in decades we’ve been able to move something from Phase 1 into Phase 3 for osteosarcoma. Q: How does philanthropy make a difference in the Developmental Therapeutics Committee’s work and where could you use more funding? Philanthropy is important in so many ways. For example, our early-phase clinical trials are supported by grants from the NCI. |
"Each of the projects Cookies for Kids’ Cancer supports represents the possibility of hope for lives saved – and hope for families who have a child with cancer is priceless. We saw first-hand, with our son Liam, the debilitating and sometimes even life-threatening side effects of cancer treatments. Our mission is to fund research that offers the potential for less toxic therapies to become available for kids as quickly as possible. And that is exactly what the Children’s Oncology Group Developmental Therapeutics Committee is doing. Seeing new therapies give families hope, and their child the future they deserve after cancer is what motivates us every day to do anything and everything we can." Gretchen Witt, Co-Founder Cookies for Kids’ Cancer |
But those grants only cover part of the cost of running those trials, which means we also need other funding sources. For more than 10 years, a foundation called Cookies for Kids’ Cancer has stepped up to help. They’ve given nearly $3.5 million to the COG Foundation to cover the gap between what we get from the NCI and how much it actually costs for institutions to conduct the trial. That means more studies are available, which could make a huge difference to families and their children. I can’t thank Cookies for Kids’ Cancer enough – their support has been pivotal.
Q: What motivates you to make research part of your career?
Very early on, I decided I wanted to do research that would make treatment better for my patients and potentially for many other patients. For example, I have a patient with osteosarcoma that I’ve treated for 10 years. Thanks in part to COG trials, the drugs we can give him today didn’t even exist 10 years ago and he’s doing extremely well. It’s incredibly gratifying to be part of this – we have a long way to go, but we’re able to offer so much more than we could just a decade ago and that’s only because of research.
Q: What motivates you to make research part of your career?
Very early on, I decided I wanted to do research that would make treatment better for my patients and potentially for many other patients. For example, I have a patient with osteosarcoma that I’ve treated for 10 years. Thanks in part to COG trials, the drugs we can give him today didn’t even exist 10 years ago and he’s doing extremely well. It’s incredibly gratifying to be part of this – we have a long way to go, but we’re able to offer so much more than we could just a decade ago and that’s only because of research.