TABLE 2.

Targeted agents in pediatric cancers

Inhibitor target	Example molecular biomarkersa	Example therapeutics	Example pediatric tumors	References
PI3K/mTOR	PIK3CA mutations PTEN loss TSC1/2 loss	Everolimus Temsirolimus Rapamycin	Sarcomas Subependymal giant cell astrocytomas	24,25
MEK	BRAF mutation BRAF tandem duplication N/KRAS mutation PTPN11 mutation NF1 loss	Trametinib Selumetinib	Melanoma Plexiform neurofibroma Glioblastoma Juvenile myelomonocytic leukemia	26,27
BRAF	BRAF V600E/K BRAF fusions	Vemurafenib Dabrafenib	Melanoma Langerhans cell histiocytosis Glioma Pilocytic astrocytomas (2nd-generation inhibitors only)	28–31
ALK	ALK mutation/fusion NTRK1/2/3 fusion ROS1 fusion	Crizotinib	Neuroblastoma Embryonal sarcomas	32,33
NTRK 1/2/3	NTRK1/2/3 fusion	Crizotinib LOXO-101	Infantile fibrosarcomas Mesonephric blastoma	34,35
SMO	PTCH1 mutation SUFU mutations GLI1 amplification	Vismodegib	Medulloblastoma	36
PARP1	BRCA1/2 mutation EWSR1-FLI fusion ATM mutation	Olaparib Rucaparib	Ewing Sarcoma	37,38
CDK4/6	CDK4/6 amplification CyclinD1 amplification	Palbociclib	Neuroblastoma Rhabdomyosarcoma ATRT	39
BET bromodomain	BRD-NUT fusions MYCN amplification MYC translocations	JQ1, IBET726, OTX015	NUT midline carcinomas Neuroblastoma Medulloblastoma Burkitt lymphoma	40,41
AURKA	MYCN amplification	Alisertib	Neuroblastoma	46
FGFR	FGFR1/2/3 fusion, amplification, mutation	Ponatinib Dovitinib	Rhabdomyosarcoma	42
Multikinase inhibitors	FLT3 mutation or internal tandem duplication	Sorafenib	Acute myeloid leukemia	43,44
	VEGFR, cKit, PDGFR expression	Pazopanib	Sarcomas	45

^aLoss refers to genomic loss through either deletion or inactivating mutation.