Selective targeting of neuroblastoma tumour-initiating cells

Selective targeting of neuroblastoma tumour-initiating cells by compounds identified in stem cell-based small molecule screens by Kristen M Smith and 16 co-authors, including David R Kaplan, EMBO Mol Med 2010(Aug 18) [Epub ahead of print][Full text]. Abstract:

Neuroblastoma (NB) is the most deadly extra-cranial solid tumour in children necessitating an urgent need for effective and less toxic treatments. One reason for the lack of efficacious treatments may be the inability of existing drugs to target the tumour-initiating or cancer stem cell population responsible for sustaining tumour growth, metastases and relapse. Here, we describe a strategy to identify compounds that selectively target patient-derived cancer stem cell-like tumour-initiating cells (TICs) while sparing normal paediatric stem cells (skin-derived precursors, SKPs) and characterize two therapeutic candidates. DECA-14 and rapamycin were identified as NB TIC-selective agents. Both compounds induced TIC death at nanomolar concentrations in vitro, significantly reduced NB xenograft tumour weight in vivo, and dramatically decreased self-renewal or tumour-initiation capacity in treated tumours. These results demonstrate that differential drug sensitivities between TICs and normal paediatric stem cells can be exploited to identify novel, patient-specific and potentially less toxic therapies.

See also: New Twist on Drug Screening to Treat Common Childhood Cancer, ScienceDaily, August 18, 2010. Excerpt:

A study led by scientists at The Hospital for Sick Children (SickKids) reveals a new method of identifying drugs to treat children suffering from fatal cancers for which an effective treatment has not been found. Rather than developing a new drug from scratch, which is a complicated and time-consuming process, they tried a different approach: in the lab, they tested existing drugs on cancer stem cells from young patients with neuroblastoma, one of the common cancers of infants and children.

A related blog post is: High-throughput cancer stem cell-based screening assay for therapeutic compounds by Alexey Bersenev, Stem Cell Assays, August 19, 2010 [FriendFeed entry].