Pathophysiologic Consequences of Survival Signaling in Neuroblastoma

Division Of Basic Sciences - Nci

Investigators

Linked publications & trials

Abstract

Aim 1. We continue to collaborate with Dr. Zhijie Li, a 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 recently 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 G-quadraplex DNA structure found within the MYCN locus. This study was recently published Yang et al Nucleic Acid Res. 2021. This work is coming to fruition and overlapping with studies detailed in Project 1. This work was negatively impacted by Covid shutdown but wet lab work is coming to a conclusion. One manuscript is under 2nd review and another is recently submitted.