Infantile Brain Tumors: A Review of Literature and Future Perspectives

Abstract

Brain tumors in infants including those diagnosed in fetal age, newborns and under a year old represent less than 10% of pediatric nervous system tumors and present differently when compared with older children in terms of clinical traits, location and histology. The most frequent clinical finding is a macrocephaly but non-specific symptoms can also be associated. The prognosis is usually poor and depends on several factors. Surgery continues to be the main option in terms of therapeutic strategies whereas the role of chemotherapy is not yet well defined and radiotherapy is exceptionally undertaken. In view of this situation, a molecular characterization could assist in providing therapeutic options for these tumors. This review highlights the recent advances in the diagnosis and treatment of brain tumors in infants with a particular focus on the molecular landscape and future clinical applications.

Keywords: brain tumors; congenital cancer; neonatal cancer; neuro-oncology; tumors in infants.

Figure 1

Molecular pathways and potential druggable targets in brain tumors of infants. (a) AT/RTs are characterized by the inactivation of SMARCB1 or SMARCA4. These molecules regulate cyclin dependent kinase inhibitor 1C (CDKN1C) through LIN28B that upregulates aurora kinase A (AURKA). (b) BRAF mutations have been detected in HGGs and LGG and BRAF inhibitors have proven effective. Gene fusions involving the neurotrophin receptor tyrosine kinase genes 1–3 (NTRK1, NTRK2 and NTRK3) have been identified in HGGs and new anti-TRK drugs are promising. (c) Inactivating mutations of PTCH1 or SUFU characterize the subgroup SHH of a medulloblastoma. As SUFU is a negative regulator of the glioma-associated oncogene (GLI) transcriptional factors that activate the Hedgehog (HH) pathway, GLI antagonists are new potential targeted drugs. (d) The loss of p16 in ependymoma leads to the activation of the p16-CDK4/6-pRB-E2F pathway, suggesting a potential role of CDK4/6 inhibitors. AT/TR: atypical teratoid rhabdoid tumor; HGG: high-grade glioma; MB-SHH: medulloblastoma, subgroup SHH; EPN: ependymoma.