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A Conversation With Drs. Bryan Wolf and Peter Adamson on Cancer Moonshot
By Bryan A. Wolf, MD, PhD, Chief Scientific Officer and Director of the Research Institute
Every space flight mission requires a carefully planned trajectory, and similarly the national Cancer Moonshot initiative needed a scientific roadmap to reach its ambitions of accelerating the prevention, diagnosis, and treatment of cancer to make a decade of progress in the next five years. In September, Peter Adamson, MD, an oncologist at the Children’s Hospital of Philadelphia and an internationally recognized leader in pediatric cancer drug development who also chairs the Children’s Oncology Group (COG), joined other thought leaders in the cancer research community as a member of the Blue Ribbon Panel (BRP) for the National Cancer Institute (NCI) to issue 13 recommendations for the Cancer Moonshot. Three of the BRP’s recommendations focus on childhood cancer. In this Q&A with Dr. Adamson, let’s take a look at how they intersect with ongoing research at CHOP.
It is a huge stride in the field of pediatric cancer for an expert in childhood cancers to have a “seat at the table” in setting national priorities for the Cancer Moonshot initiative. What unique perspectives and contributions did you share with the BRP’s pediatric cancer working group?
Despite all the progress we’ve made in childhood cancer, it remains the leading cause of death from disease in children. And for those children who do survive, more than half of them carry some lifelong consequence of their therapies. So there is an urgent need for advancements for children with cancer. It was very important that the NCI recognized that out of all the potential areas for research, childhood cancer is different. The cancers children get are different. The approaches to treatment may well be different, and the scientific opportunities may be different.
Certainly, my experience here at CHOP and my experience with the COG has positioned me well to serve as an advocate for children with cancer on the Blue Ribbon Panel. For the Panel’s pediatric working group, we assembled leaders from around the country in a very short timeframe to identify innovative areas of science today that could accelerate progress in pediatric cancer. And we’re fortunate that many of the leaders in childhood cancer research are right here at CHOP, including Stephen P. Hunger, MD, chief of the division of Oncology and director of the Center for Childhood Cancer Research at CHOP, and John Maris, MD, a pediatric oncologist at CHOP and co-head of the Pediatric Cancer Dream Team, who are pursuing new treatments for the most challenging childhood cancers. As part of the working group, they helped us focus the discussion and think about transformative research ideas.
When the BRP presented its 13 recommendations to the NCI, three focused specifically on the need to intensify research on the major drivers of childhood cancers. Could you please explain these priorities and how efforts here the Research Institute intersect with these recommendations?
One of the recommendations focuses on immunotherapeutics and cellular therapies, which harness the body’s natural defenses to fight cancer. These are exciting new approaches that are having significant impact in a small number of adult cancers and an even smaller number of pediatric cancers. We know that many of the targets to redirect the immune system are going to be fundamentally different in childhood cancers than adult cancers. At CHOP, the immunotherapy work of Dr. Maris and the Dream Team is a cornerstone that can be leveraged with experts from around the country to take a comprehensive approach to defining these unique targets. CHOP is also fortunate to have a pioneer in cellular therapy, Stephen P. Hunger, MD, to help lead future efforts in this realm.
The second recommendation is to intensify research on a fundamental change — the creation of a new protein called an oncoprotein or fusion oncoprotein — that we know drives many types of childhood cancers including certain leukemias, certain brain tumors, and a range of solid tumors including many types of sarcomas. This relatively simple molecular change can have a profound effect that turns a normal cell into a malignant cell. We have too many gaps in our knowledge about how these fusion oncoproteins are working. Of great importance is how we can develop therapies that target the fusion oncoproteins. Laboratories at CHOP are focusing on molecular drivers of childhood cancer, and our scientists will be able to participate and help lead this national effort to really understand the biology of these fusion oncoproteins and uncover novel ways of treating them.
And the third recommendation is to understand how pediatric cancers become resistant to therapy. Through a collaboration with the NCI, The Children’s Oncology Group is leading a national effort called NCI-COG Pediatric Match, which is a clinical trial for children whose cancer relapses; at the time of relapse, a biopsy will be used for genomic studies of the relapsed tumor, and then a process will attempt to match the genomic results to a potential treatment. It not only will potentially provide targeted new drugs for some of the children who we care for with relapsed cancer, but it also will be an over-arching approach to understanding what leads to cancer relapse and treatment resistance.
Upon launching the Cancer Moonshot in January, Vice President Biden called for greater collaboration in cancer research. How do the new recommendations suggest that we achieve this?
The working group recommendations call for the creation of translational science networks to address key areas of research. These networks will link leading laboratories around the country and around the world that are laser focused on these scientific challenges, as opposed to one lab working on a problem on its own. The discoveries from the laboratories will feed into the existing childhood cancer clinical trial networks, including the COG, so that we will have a smooth transition between discovery and potential treatment. That can be a long path even under the best of circumstances, but we’re aiming to compress the timeline to bring new therapeutics to the clinic at a much faster pace.
The Cancer Moonshot initiative also was designed to be a collaborative effort in that it encouraged parents, children, and childhood cancer advocacy groups to submit their input about the project’s goals. How can they continue to stay involved and use their participation as “fuel” for these research recommendations?
We have a pathway forward on some key areas that will lead to breakthroughs and new therapies, but without a substantial and sustained increase in funding to the NCI, none of what we discussed will happen. This is not going to work as business as usual. It is going to take a significant new investment on the part of our country. So perhaps the most important thing that patients, families, advocates, and others can do is to reach out to their representatives in Congress and tell them the importance of funding the Cancer Moonshot program and funding the recommendations of the BRP. There is bipartisan support to increase funding to the NIH and NCI, but it is a big step from support to actual dollars. The election may have an impact on how this will play out, but no one knows with certainty. Without the funding, there will still be research, of course, but not the transformative research that we’re looking toward.
If all goes well and the Cancer Moonshot receives the necessary appropriations to pursue its ambitious goals, in what ways do you think pediatric cancer research will be transformed five years from now?
I see a way forward to develop specific treatments for cancers that have defied targeted treatment for many years. Knowing the drivers of the cancers, but not understanding how those drivers work, and not knowing how to develop a therapy for them, is perhaps one of the more frustrating situations not only for clinicians and scientists, but most importantly for patients and families. We still use drugs developed in the 50s, 60s, and 70s to treat these cancers. If we can change the paradigm and understand how these fundamental genetic changes in the tumor lead to cancer and how we can develop a therapy towards that, then we will begin in earnest to enter an era of precision medicine that is both more effective and less toxic.
With that said, we don’t know exactly where our discoveries will lead, but by pursuing research with a focus ultimately on therapeutic development, it maximizes the likelihood that we’ll see important, novel effective approaches emerge. We will be able to go above and beyond what research is being done today and build on opportunities that may help transform the outcome for children with cancer.