New Target for the Treatment of Neuroblastoma

A new target which may be used in the therapy of neuroblastoma was identified by Scientists from University of Liverpool. This study could accelerate the development of new drugs against neuroblastoma. Their finding was published in Cancer Research.

Neuroblastoma is the most common extracranial solid tumor in children and a cancer that has a high potential to metastasize. In 40% of high-risk neuroblastoma cases, amplification of the MYCN (MYCN-A) oncogene has been found as the oncogenic event responsible for aggressive progression and poor clinic outcome. The machanisms by which MYCN promotes tumorigenesis are complex and linked primarily to its transcriptions activity,upregulating the expression of a large variety of genes involved in proliferation, survival, differentiation, DNA repair, drug resistance, and survival.

In this study, researchers have shown that altered expression of sulfotransferases in human neuroblastoma cells with higher levels of Sulf-2 expression, a specific feature of MYCN-amplified cells(MYCN-A cells) that represent a particularly aggressive subclass. Sulf-2 overexpression in neuroblastoma cells lacking MYCN amplification (MYCN-NA cells) increased their in vitro survival. They also confirmed, in two different patient cohorts, the association in expression patterns of Sulf-2 and MYCN and determined that Sulf-2 overexpression predicted poor outcomes in a nonidependent manner with MYCN.

This finding defines Sulf-2 as a novel positive regulator of neuroblastoma pathogenicity that contributes to MYCN oncogenicity.

Scientists from Cancer Research UK have discovered a new combination of drugs which could start the self-destructive process of lung cancer cells. This finding paves the way for the research on new lung cancer therapy. Their study was published in Cell Death & Differentiation.

Tumor necrosis factor-related apoptosis-inducing ligand(TRAIL) can induce apoptosis in many cancer cells without causing toxicity in vivo. However, to date, TRAIL-receptor agonists have only shown limited therapeutic benefit in clinical trials.

In this study, researchers have identified PIK-75, a small molecule inhibitor of the p110?isoform of phosphoinositide-3 kinase(PI3K) as an exceptionally potent TRAIL apoptosis sensitizer. However, PI3K inhibition was not responsible for this activity. A kinome-side in vitro screen revealed that PIK-75 strongly inhibits a panel of 27 kinases in addition to p110?. Within this panel, they identified with TRAIL effectively induced apoptosis even in highly TRAIL-resistant cancer cells. In addition, when evaluating cancer selectivity of TRAIL combined with SNS-032, the most selective and clinically used inhibitior of CDK9, they found that a panel of mostly TRAIL-resistant non-small cell lung cancer cell lines was readily killed, even at low concentrations of TRAIL.

To sum up, based on the high potency of CDK9 inhibition as a cancer cell-selective TRAIL-sensitizing strategy, the researchers envisages the development of new, highly effective cancer therapies.