Targeted therapy in pediatric and adolescent oncology.

Division of Hematology-Oncology, IWK Health Center, Halifax, Nova Scotia, Canada.
Cancer (Impact Factor: 5.2). 05/2011; 117(10 Suppl):2268-74. DOI: 10.1002/cncr.26050
Source: PubMed

ABSTRACT 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, particularly 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.

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    ABSTRACT: Immunotherapy for cancer has shown increasing success and there is ample evidence to expect that progress gleaned in immune targeting of adult cancers can be translated to pediatric oncology. This manuscript reviews principles that guide selection of targets for immunotherapy of cancer, emphasizing the similarities and distinctions between oncogene-inhibition targets and immune targets. It follows with a detailed review of molecules expressed by pediatric tumors that are already under study as immune targets or are good candidates for future studies of immune targeting. Distinctions are made between cell surface antigens that can be targeted in an MHC independent manner using antibodies, antibody derivatives, or chimeric antigen receptors versus intracellular antigens which must be targeted with MHC restricted T cell therapies. Among the most advanced immune targets for childhood cancer are CD19 and CD22 on hematologic malignancies, GD2 on solid tumors, and NY-ESO-1 expressed by a majority of synovial sarcomas, but several other molecules reviewed here also have properties which suggest that they too could serve as effective targets for immunotherapy of childhood cancer.
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    ABSTRACT: Background Technological advances including high-throughput sequencing have identified numerous tumor-specific genetic changes in pediatric and adolescent cancers that can be exploited as targets for novel therapies. Scope of review This review provides a detailed overview of recent advances in the application of target-specific therapies for childhood cancers, either as single agents or in combination with other therapies. The review summarises preclinical evidence on which clinical trials are based, early phase clinical trial results, and the incorporation of predictive biomarkers into clinical practice, according to cancer type. Major conclusions There is growing evidence that molecularly targeted therapies can valuably add to the arsenal available for treating childhood cancers, particularly when used in combination with other therapies. Nonetheless the introduction of molecularly targeted agents into practice remains challenging, due to the use of unselected populations in some clinical trials, inadequate methods to evaluate efficacy, and the need for improved preclinical models to both evaluate dosing and safety of combination therapies. General significance The increasing recognition of the heterogeneity of molecular causes of cancer favours the continued development of molecularly targeted agents, and their transfer to pediatric and adolescent populations.
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