Pathophysiologic Consequences of Neurotrophin Activation of Trk in Neuroblastoma

Division Of Basic Sciences - Nci

Investigators

Linked publications, trials & patents

Abstract

Aim 1. To investigate biologic consequences of TrkB/PI-3Kinase/AKT activation on NB tumor biology We have continued to collaborate with Dr. Zhijie Li our former fellow who is now Research Director at China Medical University in Shenyang China, to study on how activated activated survival signaling pathways affect the response of NB cells to cytotoxic drugs. To this purpose we have collaborated on several studies aimed at understanding how the PI3Kinase pathway contributes to tumor cell resistance and studies examining new agents. These studies have been published. Studies on Aim 3 to target N-myc have great potential for high-risk NB and other types of cancers with high N-Myc expression. To identify druggable N-Myc protein partners that are essential for N-Myc transcriptional and oncogenic activity, we have performed a co-immunoprecipitation (IP) and mass-spectrometry assays from NB cells. A limitation of current studies has been their use of transfected constructs into cells that normally do not express N-Myc. We have developed an interactome based on identification of the endogenous N-Myc interactors. By developing a comprehensive N-Myc interactome map, we have identified novel co-activators and co-repressors of N-Myc function. In collaborative studies with Dr. Schneekloth of the Chemical Biology Lab we analyzed a small molecule inhibitor of a unique Gquadraplex DNA structure found within the MYCN locus. This study was recently published Yang et al Nucleic Acid Res. 2021. Much of the work by the post-bacs assigned to this project was negatively impacted by the COVID shut down of the lab and virtual nature of research by some lab members, thus the majority of some investigators time was limited to data analysis and research reviews.