Precision medicine in pediatric oncology: Lessons learned and next steps

Abstract

The maturation of genomic technologies has enabled new discoveries in disease pathogenesis as well as new approaches to patient care. In pediatric oncology, patients may now receive individualized genomic analysis to identify molecular aberrations of relevance for diagnosis and/or treatment. In this context, several recent clinical studies have begun to explore the feasibility and utility of genomics-driven precision medicine. Here, we review the major developments in this field, discuss current limitations, and explore aspects of the clinical implementation of precision medicine, which lack consensus. Lastly, we discuss ongoing scientific efforts in this arena, which may yield future clinical applications.

Keywords: next-generation sequencing; oncology; precision medicine; targeted therapy.

FIGURE 1

An overview of precision medicine in oncology. Patients are enrolled for genomic profiling following informed consent. Tumor samples are then acquired, processed, molecularly profiled (typically through sequencing), and analyzed computationally. Molecular results are reviewed in a precision medicine tumor board prior to disclosure of selected, relevant results to the patient. Where available, targeted therapies may be initiated based on molecular findings

FIGURE 2

Molecular data in precision oncology. Pediatric cancers may harbor clinically relevant germline and somatic variants, copy number aberrations, gene fusions, and gene expression patterns. Here, the outer circle indicates the type of molecular event. The middle circle indicates the various molecular assays used to profile a given molecular event. The inner circle provides several examples of clinically relevant findings enabled by molecular profiling. WES, whole exome sequencing; WGS, whole genome sequencing; cDNA, complementary DNA; Mut, mutation; Amp, amplification; Del, deletion; Indel, insertion/deletion; SNV, single-nucleotide variant; aCGH, array comparative genome hybridization

FIGURE 3

Future directions in precision medicine. In upcoming years, further research may define clinical roles for multiple new areas of precision medicine. Four potential new areas include epigenomic profiling, small RNA profiling, neoantigens, and epitope profiling, and single cell sequencing and cell-free DNA (cfDNA)