Systems-level analysis of neuroblastoma tumor-initiating cells implicates AURKB as a novel drug target for neuroblastoma.
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Systems-level analysis of neuroblastoma tumor-initiating cells implicates AURKB as a novel drug target for neuroblastoma.

Clin Cancer Res. 2010 Jul 22;

Authors: Morozova O, Vojvodic M, Grinshtein N, Hansford LM, Blakely KM, Maslova A, Hirst M, Cezard T, Morin RD, Moore R, Smith KM, Miller F, Taylor P, Thiessen N, Varhol R, Zhao Y, Jones SJ, Moffat J, Kislinger T, Moran MF, Kaplan D, Marra MA

Neuroblastoma (NB) is an aggressive tumor of the developing peripheral nervous system that remains difficult to cure despite the development of aggressive chemotherapies. The poor prognosis for high-risk NB patients is associated with common disease recurrences that fail to respond to available therapies. Neuroblastoma tumor initiating cells (TICs), isolated from metastases and primary tumors, are thought to escape treatment and contribute to tumor relapse. New therapies that target the TICs may therefore prevent or treat tumor recurrences. We undertook a systems-level characterization of NB TICs to identify potential drug targets against recurrent NB. We utilized next-generation RNA sequencing and/or human exon arrays to profile the transcriptomes of 11 NB TIC lines from 6 NB patients, revealing genes that are highly expressed in the TICs compared to normal neural crest-like cells and unrelated cancer tissues. We used gel-free two-dimensional liquid chromatography coupled to shotgun tandem mass spectrometry (MudPIT) to confirm the presence of proteins corresponding to the most abundant TIC-enriched transcripts thereby providing validation to the gene expression result. Our study revealed that genes in the BRCA1 signaling pathway are frequently missexpressed in neuroblastoma TICs, and implicated Aurora B kinase as a potential drug target for NB therapy. Treatment with a selective AURKB inhibitor was cytotoxic to NB TICs but not to the normal neural crest-like cells. This work provides the first high resolution systems-level analysis of the transcriptomes of 11 primary human NB TICs and identifies a set of candidate NB TIC-enriched transcripts for further development as therapeutic targets.

PMID: 20651058 [PubMed - as supplied by publisher]

Read the complete post at http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&db=PubMed&cmd=Retrieve&list_uids=20651058&dopt=Abstract

Posted 24 Jul 2010 4:16 AM by pubmed: neuroblastoma
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There is nothing quite as devastating as hearing that word - neuroblastoma. In seconds your world is turned upside down and your normal life is but a distant memory. You are thrust into a confusing world full of fear. Your child has cancer.

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Welcome to our website. It is a place for you to find answers and ask questions. One of the primary goals of the Neuroblastoma Foundation is to ensure that parents, patients and health care professionals find the information they need to make the best treatment decisions possible for children and adults affected by neuroblastoma. There is a vast amount of information throughout the internet, much of which is encapsulated in medical jargon that is so complex that even many medical professionals have difficulty in interpreting its meaning. We are here to help to decipher this information and to make sure you (and your oncologist) understand exactly what it means to you. From treatment decisions to side effects we have parents and experts that have experienced it all and are willing to distill it for you.