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More resources are needed for pediatric cancer research

David A. Williams, MD
Conditions
November 20, 2014
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The fact that childhood cancer is, thankfully, a rare disease belies the fact that it is the leading cause of disease-related death in U.S. children, age 1 to 19.  The fact that it is a rare disease also belies the fact the number of people with a direct stake in expanding research into pediatric cancer is quite large and extends well beyond the small number of children with cancer and their families. Not only are the combined life-long contributions of children cured of cancer enormous, but understanding cancers of young children could also hold the key to understanding a broad range of adult cancers. The time is ripe to allocate more resources, public and private, to research on pediatric cancer.

In an age of increased understanding of the genetic basis of diseases, one thing is striking about many childhood cancers. They are relatively “quiet” cancers, with very few mutations of the DNA. The young patients haven’t lived long enough to acquire the large number of mutations that create the background “noise” associated with years of living. This makes it much easier to pinpoint the relevant genetic abnormalities in a young child’s cancer.

Add to this the growing realization that biology, including how various tumors use common “pathways,” not the malignancy’s location in the body, is a major factor in how the cancer responds to treatment. Thus, a mechanism that’s relatively easier to observe in the cancers of young children could help scientists understand cancers in adults in which the same mechanism is hidden amid the clutter of mutations acquired over a longer life. Unlocking the secrets of a rare pediatric brain tumor, for instance, could help unlock the secrets of lung cancers that share the same biology – and provide an elegantly narrow focus in the search for more effective treatments of both. This turns on its head the current conventional paradigm of discoveries in adults slowly making their way to children.

Ewing sarcoma, a rare pediatric cancer of the bone, is one such “quiet” tumor, with very few gene mutations associated with the malignant cells. Researchers have discovered that one gene mutated in a subset of Ewing sarcoma tumors is also mutated in other cancers — including some forms of leukemia, pancreatic cancer, brain tumors and bladder cancer. Now, in a study recently published in the journal Cancer Discovery, my colleagues at Dana-Farber/Boston Children’s Cancer and Blood Disorders Center report that in Ewing sarcoma, this mutation is associated with the metastatic process, the means by which malignant cells spread throughout the body, thus opening the door to a better understanding of this process both in Ewing and other more common malignancies.

Another example is retinoblastoma, a cancer of the eye that most often affects children under age 2. Almost 30 years ago, when our understanding of gene mutations associated with cancer was in its infancy, scientists found that a gene that normally controls cell growth — a so-called “suppressor” gene — was mutated in retinoblastoma and that this mutation causes the disease. The same mutation was later found to be present in several other cancers, and the discovery proved to be critical not only for retinoblastoma but also for understanding the process of tumor suppression itself. This gene was the first of a number of other tumor suppressor genes that, when mutated, can contribute to many adult cancers.

Research from other colleagues into rare early childhood cancers of the brain and kidney called rhabdoid tumors is generating interest in the scientific community well beyond the small number of patients who develop the diseases. The driving mutation in these tumors affects a complex of proteins now understood to be mutated in 20 percent of all cancers. This includes some cancers of the ovary, lung, brain, colon, liver, stomach, pancreas, kidney, esophagus and bladder, among others.

My fellow scientists and I stand on the shoulders of researchers before us — including those whose pioneering work on chemotherapy for children with cancer has benefited patients of all ages. Indeed, for the most common types of childhood leukemia, the large majority of children are now cured of their disease. Helping children who still succumb to cancer, despite the dramatic progress made over the past several decades, should be reason enough to increase funding for research into childhood cancer. That the research may also benefit large numbers of adults only makes increased support that much more imperative.

David A. Williams is chief, hematology/oncology, Boston Children’s Hospital and associate chairman, pediatric oncology at Dana-Farber Cancer Institute. This article originally appeared in the Huffington Post.

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