Study sheds new light on aggressive childhood cancer
EU-funded researchers have uncovered some of the complex molecular mechanisms that drive the growth of neuroblastoma, a type of cancer found in very young children. The scientists hope that their findings, published in the journal Cancer Cell, will lead to the development of new therapies to treat this often aggressive and unpredictable disease.
EU support for the study came from the IMPACT (Identification of novel targets for cancer therapy) project, which is financed through the 'Life sciences, genomics and biotechnology for health' Thematic area of the Sixth Framework Programme (FP6).
Neuroblastoma is a cancer of the nervous system that primarily affects children under the age of five years. During normal development, neural crest cells stop dividing and turn into different types of mature nerve cells. However, in neuroblastoma, this does not happen and the cells simply keep dividing, forming a tumour.
The tumour most commonly develops in the abdomen, often in the adrenal glands or the nerve tissue towards the back of the abdomen. However, it can also spread to other parts of the body through the blood and lymphatic system. Symptoms vary depending on where the disease is located and whether it has spread to other parts of the body. Because the symptoms are often vague (including tiredness, fever and loss of appetite) in the early stages of the disease, neuroblastoma is often difficult to diagnose.
Previous work has shown that high levels of a gene called MYCN are often linked to treatment resistance and poor prognosis. MYCN disrupts the control of cell division and differentiation. The researchers analysed 194 other genes that are either dependent on high levels of MYCN activity in the neuroblastoma cells or are targeted directly by genes of the Myc family.
They found that a gene called AURKA is required for the growth of MYCN-amplified tumours, but is not needed by cells lacking amplified MYCN. AURKA is a well-known cancer gene that has already been implicated in the growth of other types of tumour in humans.
The AURKA gene codes for an enzyme called Aurora A that binds to and stabilises N-Myc, and the researchers suggest this in turn contributes to the development of neuroblastoma by interfering with the maturation of developing nerve cells. The researchers also found that Aurora A's ability to stabilise N-Myc is not linked to its enzymatic properties. Therefore, potential drugs designed to block its enzymatic properties may not block its interactions with N-Myc.
"Our results show that stabilisation of N-Myc is a critical oncogenic function of Aurora A in childhood neuroblastoma; the challenge will now be to find ways to interfere with this function in order to find new approaches for the therapy of these tumours," commented Dr Martin Eilers of the University of Würzburg in Germany. "The findings also suggest that the current views about why Aurora A is oncogenic may need to be re-evaluated."
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