Towards a turning point of neuroblastoma therapy

Abstract

In 1983, the MYCN oncogene amplification was discovered in neuroblastoma cells and few years later its prognostic role was clearly demonstrated. The first European study, in which MYCN gene status is taken as prognostic factor for therapeutic decision, was released by SIOPEN and GPOH in 1995. Afterward, other trials were released by SIOPEN, GPOH, COG, and JNBSG in which MYCN gene amplification was employed as prognostic risk factor. However, since MYCN is abnormal in about 20% of tumors and is a reliable prognostic marker for only some subgroups of patients, additional chromosomal abnormalities have been introduced for clinical decisions: 1p deletions/imbalances (GPOH), 11q deletions/imbalances (COG), and structural copy number aberrations (SIOPEN). MYCN gene status and chromosome aberrations improved patients' risk evaluation and helped to develop tailored therapy for diverse subgroups of patients. Unfortunately, high risk patients still have an unfavorable prognosis and are the major challenge for oncologists. In the last decade, the advent of genome-wide analysis and the next generation sequencing technique have given the opportunity to deeply investigate the genome of neuroblastoma to identify both candidate genes associated with tumor progression and druggable target genes. ALK gene is an actual candidate for the therapy with small molecule inhibitors, but others as mTOR, Aurora, and TRK, are suitable targets for subgroups of high risk patients. The huge amount of clinical and biological information collected in the last 20 years suggests that it is time to turn on for new and more personalized therapies of neuroblastoma.