Four Things on the Horizon in Childhood Cancer
By Lisa Diller, MD, Chief Medical Officer, Dana-Farber/Boston Children’s

The 20th
century saw striking advances in curing childhood cancer, primarily as a result
of the discovery that broadly toxic chemotherapy agents could kill malignant
cells. As a result, pediatric cancer, once a virtually incurable disease, now
enjoys an overall long-term survival rate that tops 80 percent. In the 21st
century, attention is turning to newer agents that promise to open additional,
less toxic avenues to cure. For Childhood
Cancer Awareness Month 2015, here are four things on the horizon for
pediatric cancer.
Precision Medicine
Treatment for cancers
is now being transformed because we can genetically characterize an
individual’s tumor, finding genetic changes that suggest specific targeted
therapies. These therapies are developed
for specific targets that may be implicated in a wide variety of pediatric and
adult cancers. A cancer’s biology,
rather than its location in the body or the age of the patient, becomes the
salient factor. Drugs that are proving effective at treating an adult lymphoma,
for instance, can also treat a pediatric solid tumor with similar biologic characteristics. Likewise, a discovery
in pediatric cancer can open new avenues of treatment for adult cancers.
Still,
there are barriers to overcome in bringing these discoveries to children with
cancer. We need drugs in liquid form for young children, yet many drugs are
being developed only as pills. We need preclinical testing in pediatric models and
efficient early phase trials to establish the appropriate dosing for children.
We must recognize that some pathways implicated in the development of a
childhood cancer might be different from the pathways indicated in adult
cancers, but there may still be crossover in terms of the therapeutic agents
themselves. Pediatric cancers often involve changes in the epigenome – or in gene
regulation – rather than mutations or abnormalities in gene sequencing. The
question is can we use the same pathways being used in precision medicine to
target epigenetic changes. >>More about precision cancer medicine
Immunotherapy
Immunotherapy is another new approach generating
excitement in the treatment of pediatric and adult cancers. The Food and Drug
Administration recently approved Unituxin™
(dinutuximab), an antibody agent for high-risk neuroblastoma, making it the first immunotherapy drug for
pediatric cancer to earn FDA approval. Meanwhile, promising pediatric trials
are underway for an immunotherapy approach that genetically modifies a
patient’s T-cells to recognize tumor cells in treatment-resistant leukemia.
There is a lot of enthusiasm about similarly modifying the immune system’s
T-cells to treat other cancers.
Exciting advances are being made in adult
oncology in immune checkpoint blockade therapy that uses drugs to teach a
patient’s own immune system to recognize and reject tumor cells. Already there
have been dramatic advances in melanoma outcomes and promising results in other
adult-onset cancers. We are beginning to learn how to use this approach in
pediatric cancers. There is also a lot of interest in looking at specific
cancers whose genetic mutations may act as “neoantigens,” or new antigens, suggesting
another potential avenue for immunotherapy. >>More about immunotherapy
Reducing Toxicity
The improved cure rates that characterized the last
half of the 20th century came at a cost, as chemotherapy and
radiation often have long-term negative effects that appeared as more treated children
survived into adulthood. Many developed serious chronic conditions, including
heart disease, infertility and secondary malignancies. Since the late 20th
century, we have increasingly sought ways to reduce the toxicity of treatment
to maintain cure rates with fewer late effects. These efforts will
continue.
Both targeted therapies and
immunotherapy are promising not only because of their potential curative powers
but also because they are potentially less toxic than standard chemotherapy.
Clinicians also continue to explore ways to reduce radiation, as well as to make
it more targeted to the tumor and involve less normal tissue. We will likely have information, in the years
to come, that will predict who is at higher risk for specific toxicities. This
may help clinicians, parents and patients make decisions about best therapies,
factoring in not only the likelihood of cure but also issues around long-term
quality of life. >>More about reducing toxicity
Global Health
The strides in improved cure rates in North
America and Europe have often not reached the developing
world. Meanwhile, as improved health care systems reduce the risk of childhood
death from malnutrition, diarrhea and infectious diseases, resources in developing
countries can be directed toward the care of children with cancer. Today,
clinicians in the United States, Canada and Europe are working with clinicians
in Latin America, Africa and parts of Asia to improve outcomes.
Because pediatric cancers are rare, pediatric oncology is a global community accustomed
to collaborating internationally, which offers a good platform for a stronger
focus on improving survival of childhood cancer globally. Understanding the patterns of cancer
throughout the world and differences in incidence in different countries may
bring insights into understanding the causes of childhood cancer, as well. >>More about global health