A combination of substances, which acts on the chemical modification of DNA in tumors is a new treatment for neuroblastoma aggressive forms. The new method is proposed by researchers at the Karolinska Institute, Sweden, after experiments with rodents. Combined treatment resulted in suppression of tumor growth. A study published in the PNAS, also casts doubt on the hypothesis in the research on potentially improper treatment of children with neuroblastoma.
Neuroblastoma affects the peripheral nervous system in children and is a neoplastic disease. Some of these tumors disappear naturally, while others respond well to treatment. However, there are some types of neuroblastoma, which is very aggressive and does not respond to therapy. Mortality among these patients is high, and therefore the need for new and effective treatments.
During the study, the researchers treated mice with a substance AZA, that blocks and eliminates methyl groups from the DNA of cancer cells aimed at the activation of genes that are struggling with the origin of neuroblastoma. AZA then combined with the treatment with retinoic acid, a substance that is able to differentiate certain tumor cells into harmless nerve cells.
Individually, neither AZA, neither retinoic acid could inhibit the growth of high-risk tumors, but the combination treatment resulted in a significant suppression of tumor growth in mice.
Researchers tested the combination of substances with inhibitor HIF2. Such inhibitors have been proposed as an alternative treatment for neuroblastoma, as previously HIF2 protein has been described as being associated with more aggressive forms of neuroblastoma. HIF2 inhibitor undergoing clinical trials for treatment of otherneoplastic disorders .
"It was found that the effect of combined treatment with retinoic acid and AZA was actually resistance HIF2 inhibitor. Analysis of large volumes of patient data shows that HIF2 not associated with aggressive types of neuroblastoma, but may be associated with a lower risk and improved survival for patients, "- explains Johan Holmberg, a researcher at the Karolinska Institute.
"The role played by HIF2 inhibitors requires further study before they can be used for the treatment of patients with neuroblastoma - scientists confirm -. The study is important for future clinical applications," - says Johan Holmberg.
The work was funded by the Swedish Cancer Society, the Swedish Foundation for childhood cancer and the Swedish Research Council.