Targeted Therapy in Pediatric and
Mark L. Bernstein, MD1,2
Cancers in children and adolescents are fortunately infrequent. Overall, cure rates are good, approximately 80%, although
this varies by histology and stage. Targeted therapies aim to improve efficacy and decrease toxicity by more specifically
affecting malignant cells or their supporting stroma. Cancers of early life are often of different histology than those seen
in adults. Sometimes, the same pathway is affected, even if the histology is different. Toxicities may also be different, par-
ticularly in younger children. These factors render drug development in young people challenging. This article reviews
some successes and challenges to that development, including brief discussions of imatinib, lestaurtinib, antiangiogenesis,
and anti-GD2 therapies. Cancer 2011;117(10 suppl):2268–74. V
C 2011 American Cancer Society.
KEYWORDS: targeted therapy, pediatrics, adolescence, imatinib, lestaurtinib, bevacizumab, ch14.18.
Targeted therapy aims to more selectively attack the cancer cell or its immediate supportive environment, sparing
normal tissues and therefore causing fewer side effects in the host as compared with traditional cytotoxic chemotherapy.
This review will briefly discuss some examples that highlight successes at incorporation of targeted therapy in pediatric
and adolescentoncologyas wellasother examplesthathighlightsomeof theassociatedchallenges.
In Canada, annually there areapproximately 850 new cases of cancer diagnosed in patients up to the age of 15 years,1with
another 450 cases in adolescents 15 to 19 years of age. The adolescent cases number among the approximately 2000 cases
diagnosed each year in Canadian youth between the ages of 15 and 29 years.2The population of the United States is
approximately 10? that of Canada, and the number of malignant diagnoses in children, adolescents, and young adults is
similarly approximately 10? the Canadian figure. In children and adolescents, acute leukemia accounts for around 25%
of cases. It is more frequent and more commonly lymphoid in younger patients. Central nervous system tumors and lym-
phomas each include another 25% of patients, with the remainder comprised of neuroblastomas mainly in infants and
toddlers, Wilms tumor mainly in toddlers, bone sarcomas predominantly in adolescents, soft tissue sarcomas in both pop-
ulations, and amiscellany of other diseases. Mortalitydeclined steadily from the mid-1970s through the late 1990s,witha
less steepdecline morerecently. Thisis particularly trueof thesolidtumors(Fig.1).
The goals of incorporating novel targeted agents include both an increase in efficacy, especially for those diseases
that remain of poor prognosis, and a decrease both in the short-term toxicities, such as myelosuppression, infection, nau-
sea, and vomiting, and in long-term toxicities, including neurocognitive impairment, infertility, cardiovascular morbidity
and mortality, obesity, and second cancers. Targeted therapy is based on several findings. Some changes are unique to the
malignant cells; for example, the product of the bcr/abl translocation in Philadelphia chromosome positive (Ph1þ) leuke-
mias or the ews/fli1 translocation in Ewing sarcoma. Some pathways are more prominent in malignant tissues, and some
may be important in cancers across a broad age range. These include the insulin growth factor receptor and angiogenesis path-
although they are not specific for only tumor tissue. These cell surface markers may or may not be the same in tumors across
DOI: 10.1002/cncr.26050, Received: September 20, 2010; Revised: November 25, 2010; Accepted: December 7, 2010, Published online April 27, 2011 in Wiley
Online Library (wileyonlinelibrary.com)
Corresponding author: Mark L. Bernstein, MD, Division of Hematology-Oncology, IWK Health Center, 5850/5980 University Avenue, Halifax, Nova Scotia, Canada
B3K 6R8; Fax: (902) 470-7216; firstname.lastname@example.org
1Division of Hematology-Oncology, IWK Health Center, Halifax, Nova Scotia, Canada;2Department of Pediatrics, Dalhousie University, Halifax, Nova Scotia, Canada
The articles in this supplement represent presentations and discussions at the ‘‘International Workshop on Adolescents and Young Adults with Cancer: Towards
Better Outcomes in Canada’’ that was held in Toronto, Ontario, March 11-13, 2010.
*Workshop on Adolescents and Young Adults with Cancer: Towards Better Outcomes in Canada, Supplement to Cancer.
May 15, 2011
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