LONDON – A new study has given hope that it may one day be possible to develop a specific treatment for neuroblastoma, which is a rare type of childhood cancer.

Researchers in Sweden have shown that blocking the function of a molecule that is overexpressed in neuroblastoma cells can shrink tumors and prolong survival in a mouse model of that disease.

A similar strategy may also work for many other cancers, the scientists suggested, because the molecule that is overexpressed in neuroblastoma is closely related to one that is overexpressed in more than half of all human cancers.

Marie Arsenian Henriksson, professor of molecular tumor biology at the Karolinska Institute in Stockholm, Sweden, told BioWorld Today: "There is an urgent need for new therapies for neuroblastoma. Our work shows a new approach to therapy, and the same approach could be applied to other human tumors."

Neuroblastoma is rare – in the U.S., about 800 children are diagnosed with it each year, most of them younger than 2. The tumors develop in tissues of neural origin, often in the region of the spinal cord. Frequently, the tumors consist of undifferentiated cells; treatments include surgery, radiotherapy and chemotherapy, with some therapies aiming to "push" the undifferentiated cells into differentiating into mature neurons. Once the cells have differentiated, they are no longer malignant.

Arsenian Henriksson and her collaborators were aware that tumor cells from particularly aggressive forms of neuroblastoma contain many extra copies of the gene encoding a protein called MYCN. "There are often 80 or 100 copies of this gene in each tumor cell," she said, "and these extra copies are a strong signal that the child has a poor prognosis." Only a minority of children survive those highly aggressive forms of neuroblastoma.

Such observations fit in with many other studies showing that genes encoding other proteins of the MYC family, such as c-MYC, also are present in multiple copies or overexpressed in many other types of cancer. Furthermore, much research has shown that blocking MYC proteins can cause tumors to regress in animal models.

Among those studies were some showing that a small molecule called 10058-F4 (F4) could interfere with the binding of c-MYC to another molecule called Max. Arsenian Henriksson said: "As the c-MYC protein is very similar to MYCN, we thought we should investigate its effect on MYCN, because no one had done this before."

When the researchers added F4 to cultured neuroblastoma cells in the laboratory, they found, encouragingly, that the cells differentiated into neurons. Furthermore, they were able to show that MYCN expression was down-regulated as a result of adding F4.

Next, the team wanted to find out whether they could detect an effect of F4 on two different mouse models of neuroblastoma. "We found that there was a small but significant effect," Arsenian Henriksson said. "The tumors did form even with treatment, but the mice survived a bit longer than mice which received a control treatment."

Arsenian Henriksson and her colleagues reported their findings in a paper in the June 3, 2013, issue of the Proceedings of the National Academy of Sciences, in a paper, titled "MYC inhibition induces metabolic changes leading to accumulation of lipid droplets in tumor cells."

F4 cannot be considered a potential therapy, not least because it has a very short half-life, Arsenian Henriksson said. "However, we think that it should be possible to develop another molecule that has a similar mechanism of action, which disrupts the binding between MYCN and Max. Our study provides proof of principle that it is possible to use a small molecule that targets this interaction, and I hope that researchers with the appropriate expertise will go ahead and develop a better molecule," she added.

Serendipitously, the Swedish team also observed that when F4 was added to the neuroblastoma cells, the treatment caused an accumulation of fat droplets inside the cells.

"This is an original finding," Arsenian Henriksson said. "It has not previously been observed that the inhibition of MYC affects tumor cells in this way. This not only opens new avenues for novel therapies for certain forms of cancer, but may also have implications for metabolic diseases, such as diabetes."

The researchers already are investigating whether they can replicate their observations of the lipid droplets in a model of lymphoma.