Depending on the type, location, and grade of their disease, cancer patients today are offered a menu of treatment options from which to choose—various pharmacological interventions, surgeries, chemotherapy and radiation therapies, cutting edge immunotherapies, and experimental treatments that were unthinkable even 20 years ago. Many will survive.
Survival, however, is a relative term, especially in the context of pediatric oncology. One of the greatest challenges facing researchers is how to explain the high mortality rates of and life-altering complications encountered by patients five, 10, and even 20 years after they are declared “survivors” of the cancers for which they were treated as children. In a forum conducted on September 15, 2017 in Washington, DC, reporters from The Atlantic interviewed representatives from the National Cancer Institute, Nationwide Children’s Hospital, and a host of other research institutions as well as pediatric cancer organizations, patients, and their families. They each sought to bring to wider attention the need for more research, research that could improve the post-treatment outcomes of pediatric oncology patients. Statistics can help explain both the progress that’s been made and the amount of work that remains: More than 95 percent of pediatric cancer survivors will have significant health problems by the time they reach 45 years of age. About 30 percent will die within 30 years of diagnosis. Those who survive beyond five years are eight times likelier to die because of their increased risk of liver and heart disease, in addition to their elevated risk of cancer reoccurrence.
The scientific and medical communities, if armed with the requisite tools in the form of adequate funding and the freedom to use animal models necessary for the study of childhood cancers, will find the answer. Because of the national investment in research and the strides made possible by studies with laboratory animals, 98 percent of children with acute lymphoblastic leukemia will go into remission within weeks of starting treatment. There is every reason to believe the problems encountered by today’s pediatric oncology researchers will, eventually, also be solved by these means.
CHILDHOOD CANCER: NO LONGER A DEATH SENTENCE
Provided that of the 15,700 children who test positive in cancer screenings each year the average is only six years old, physicians in most cases discuss the prognosis and treatment options instead with the patient’s parents. Cancer was once so feared, and so deadly, that often even adult patients undergoing chemotherapy and radiation treatments were not told the name of their disease. Such an abundance of caution was taken by hospital administrators to protect the privacy of oncology patients that bills were customarily delivered in unmarked envelopes. Healthcare providers could not be sure that even the patient’s immediate family members knew they had cancer.
Precautionary measures were codified into federal law. The 1966 Freedom of Information Act includes “treatment for cancer” in a clause exempting from disclosure information considered “an unwarranted invasion of personal privacy.” And until 2001, the disease’s definition in the Oxford English Dictionary spelled near-certain death. “A tumour,” read the entry until it was amended, “that tends to spread indefinitely and to reproduce itself and also to return after removal; it…generally ends in death.”
Of course, the dramatic increase in survival rates for cancer have changed the way in which families, healthcare practitioners, and researchers talk about—and think about—the disease. It seems difficult to reconcile the experiences of patients in the past with the societally and culturally reinforced messages of empowerment and support offered today to people living with cancer. This month, 5Ks, walks, hikes, marathons, and other events are scheduled in cities across the country in honor of Childhood Cancer Awareness Month, an observance sponsored by CureSearch for Children’s Cancer. The success of campaigns designed to raise awareness about cancers that affect children, and the broad public support for charities that aid pediatric oncology patients and their families, are traceable in large measure to the realistic promise of cures and more effective treatments—which rely, in many cases, on research conducted with animal models by scientists including those who work for (or are funded by) CureSearch.
The earliest breakthrough in cancer treatment, chemotherapy, was developed by studying the effects of an engineered mustard-nitrogen compound on lymphomas (cancers of the immune system) in mice. Its effectiveness in reducing the size of cancerous tumors in animals and human patients led to its adoption as a primary cancer-fighting agent, usually in combination with other therapies—including, commonly, radiation.
The lingering post-treatment effects experienced by cancer patients, especially children, are poorly understood in part because radiation therapy was not developed with many animal models. Researchers and clinicians have drawn attention in recent years to the need for additional preclinical animal studies to better determine how radiation affects living organisms as they age, both by itself and when used in combination with other treatments.
Another major focus of the scientific and medical research communities in recent years has been the promise of a relatively-new treatment called immunotherapy. It works by using the patient’s immune system to target and attack cancer cells. The first successful study, in 1984, showed that by blocking a protein receptor called CTLA-4, T cells in the immune systems of mice could destroy cancerous tumors. The treatment has been adapted for use in both human and animal patients—and represents an exciting new frontier of pediatric cancer research.
ANSWERS ABOUT METASTASIS
Why do malignant cancer cells and tumors come back with a vengeance in some patients whose disease has gone into remission while other “survivors” remain cancer-free? Researchers now understand how cancer cells “shed” and circulate into the bloodstream, settling in new locations in the body, but what causes them to awaken from dormancy in some patients but not in others? New avenues of research have focused on what is sometimes called an “ecological approach” to cancer, whereby scientists consider how the genetic makeup and environments of individual patients may portend the outcomes of their treatment.
As it was explained by Siddhartha Mukherjee, MD, writing in the New Yorker, one could think about the “ecological approach” this way: Organisms become “invasive species” in some environments but not in others. Whether they take over and threaten the ecosystems to which they’re introduced depends on a variety of factors—factors tethered to the conditions of the environments to which they are alien. These novel approaches will depend on animal experiments whose results could forever change the way cancer is studied and understood, potentially leading to more effective and less taxing treatments.
Precision medicine, an area of new research that is also focused on developing new treatments tailored to individual patients, presents a wealth of opportunities to glean more information about the safety and effectiveness of medications used to treat cancer in children. Researchers at the Jackson Laboratory are transplanting cancerous tumors into strains of mice, which has allowed them to “correlate cancers to precise genetic sequences and mutations in the human genome.” The information is compiled in a database that, scientists hope, will soon enable clinicians to select the treatment options proven most effective for patents based on their individual DNA sequences.
The value of this work almost cannot be overstated, considering the grim realities faced by childhood oncology patients—the life-altering and life-threatening after-effects of treatment, as well as the risk of malignancy from either their primary cancers or new secondary cancers. Dr. Mukherjee explained several recent animal studies that showed tremendous promise in uncovering answers through approaching cancer with an ecological lens. Among these, the work of David Adams, PhD, of the Wellcome Trust Sanger Institute, a British genomics and genetic research institute:
“Just a few yards from my office, there is an animal vivarium filled with hundreds of genetically altered mouse strains,” Adams said. “Researchers were using these strains to study the effect of these gene variants on the heart, or on the nervous system. I thought I would ask a somewhat different question: If we implanted these strains with the same cancer, which strains would permit the metastases to grow, and which ones would suppress metastatic outgrowth?”
It was an ingenious inversion of a classic experimental strategy. For decades, biologists have been altering a cancer cell’s genes and injecting the cells into a few standardized strains of mice. The “different cancers into same strain” experiments have allowed cancer biologists to observe how alterations in cancer genes might affect their growth, metabolism, and metastasis. But what effects might variations in the host’s genome have? Adams’s “same cancer into different strains” experiment switched the locus of attention from seed to soil.
The tone and tenor of the conversation at the Atlantic Live: Children and Cancer forum was similarly optimistic. Researchers, elected officials, pediatric cancer survivors, and their families discussed the “Cancer Moonshot” goals in realistic terms—while noting the importance of prioritizing research, and the need to bolster public support for cancer studies to make possible the breakthroughs that lie on the horizon. As in the past, the role of preclinical work, of studies with animal models, is inextricable from the new approaches to research that can save and improve the lives of millions of people, including the youngest and most vulnerable.