Abstract IA04: Neuroblastoma as a paradigm of MYC(N) driven cancers

Neuroblastoma is an enigmatic childhood cancer with phenotypes ranging from spontaneous regression of seemingly advanced disease to relentless metastatic progression. MYCN amplification was defined as a powerful predictor of metastatic potential and acquisition of therapy resistance in the 1980's, and arguably was the first genomic biomarker utilized in routine clinical practice to stratify therapeutic intensity. While there have been incremental improvements in cure rates over the last three decades, these have come at the cost of a highly complex and intensive chemoradiotherapeutic regimen that leaves survivors with significant long-term morbidity. Here we will discuss our ongoing efforts to define the genetic basis of neuroblastoma, and recent insight into how heritable DNA variation influences neuroblastoma susceptibility and clinical phenotypes, including MYCN amplification. We will also discuss the major oncogenic drivers of high-risk neuroblastoma beyond MYCN, including recent insights into the role of MYC in the MYCN-non-amplified high-risk cases, as well as the major role of the ALK oncogene, often in cooperation with MYCN. Finally, we will discuss recent efforts to leverage this information therapeutically, with a focus on how therapeutically targetable oncogenic pathways evolve under the selective pressure of chemoradiotherapy. Finally, we will discuss nascent efforts to deliver on the holy grail of neuroblastoma translational research—targeting the MYCN onco...
Source: Molecular Cancer Research - Category: Cancer & Oncology Authors: Tags: Myc in Human Cancers: Oral Presentations - Invited Abstracts Source Type: research