New combination treatment enables complete tumor regression in mice with high-risk neuroblastoma

In mice with high-risk neuroblastoma, tumors disappeared in response to a new combination treatment with precision medicines, a recent study from University of Gothenburg researchers shows. This is a vital step toward a potentially curative treatment for a form of cancer affecting young children that is currently difficult to treat.

The study, published in the journal Nature Communications, is the result of collaboration between researchers from the Universities of Gothenburg, Sweden and Ghent, Belgium.

Neuroblastoma is a form of childhood cancer that affects the peripheral nervous system (PNS) -; that is, the system excluding the brain and spinal cord. In Sweden, 20–30 children are diagnosed annually. The cancer may start in the adrenal glands, for instance, but tumors can occur throughout the body.

In some cases, the disease can heal and disappear by itself, but aggressive forms of neuroblastoma have a more unfavorable prognosis. The present treatment regimes are very hard for childre to undergo and side effects can have consequences for the rest of their lives.”

Ruth Palmer, Professor of Molecular Cell Biology, University of Gothenburg

Ruth Palmer leads one of the research groups behind the new study.

Tumors disappeared in mice

The study shows that a treatment combining two different precision medicines, an ATR inhibitor and an ALK inhibitor, eliminates neuroblastoma growth in mice.

“After 14 days’ treatment, the tumors had completely vanished in two independent mouse models. One of the mice relapsed after 200 days, which is a very long time for a mouse, but all the other mice are still alive,” says Dan Emil Lind, researcher in the group and one of the publication’s first authors.

“We’re surprised by the very positive result. It’s remarkable that a two-week protocol that combines these two precision medicines can lead to complete tumor regression in two separate mouse models of neuroblastoma,” says the other first author, Joanna Szydzik, a PhD student in the group when the work was done.

Follow-up underway

“In experiments in culture with human cell lines, we see the same RNA and protein expression patterns as we do in mice treated with this new regime, showing we’re on the right track,” says Jimmy Van den Eynden of the Cancer Research Institute at Ghent University, who led the Belgian part of the work.

To date, the research group does not precisely understand why this combination treatment works so well. However, an important part of their hypothesis is that the mouse immune system received signals from the tumor cells that caused the natural immune cells to infiltrate and destroy the tumor cells.

“Our results are beyond our expectations. We’ve now started a follow-up with other ATR inhibitors to investigate how they affect the mouse immune system. We want to understand why this combination treatment with precision medicines against ATR and ALK is so good,” Palmer says.

Imbalanced expression

The molecular mechanisms whereby neuroblastoma arise are only partly known. What probably occurs is that defects appear in the development of the PNS, resulting in an imbalance that favours formation of neuroblastoma. The underlying defects in the cell may be that an important gene has been lost, that there is overexpression and/or activation of a specific protein, or that a particular protein or gene has mutated.

A quarter of all high-risk neuroblastomas arise when the oncogene MYCN is overexpressed. In many cases, this overexpression occurs in combination with an increase in the activity of the ALK protein. When such oncogenes are expressed and active in a cancer cell, it tends to divide faster, and “replication stress” can then occur.

More options needed

The results from this study suggest that patients with neuroblastoma, and especially those in high-risk groups where the combination of the MYCN and ALK genes lead to replication stress, may benefit from drug treatment with ATR inhibitors.

“The drugs slow down cancer growth, but don’t fix the fundamental defect. So additional treatment options are needed for high-risk neuroblastoma driven by the ALK and MYCN oncogenes,” Palmer concludes.

Source:

Journal reference:

Szydzik, J., et al. (2021) ATR inhibition enables complete tumor regression in ALK-driven NB mouse models. Nature Communications. doi.org/10.1038/s41467-021-27057-2.

Baby News

Related Posts

Should my child attend a funeral?

Comments Off on Should my child attend a funeral?

Research reveals increase in prescriptions of specialized infant formula

Comments Off on Research reveals increase in prescriptions of specialized infant formula

Children’s noses better at inhibiting SARS-CoV-2 infections than adults

Comments Off on Children’s noses better at inhibiting SARS-CoV-2 infections than adults

Babies and sleep: The ultimate guide

Comments Off on Babies and sleep: The ultimate guide

Healthy diet interventions targeting parents of young children could provide benefits for both

Comments Off on Healthy diet interventions targeting parents of young children could provide benefits for both

Harmful effects of SARS-CoV-2 infection in pregnant women and their newborns

Comments Off on Harmful effects of SARS-CoV-2 infection in pregnant women and their newborns

Experts warn about the advertising of ultra-processed food for children on Youtube

Comments Off on Experts warn about the advertising of ultra-processed food for children on Youtube

Should pregnant women be included clinical trials?

Comments Off on Should pregnant women be included clinical trials?

SARS-CoV-2 transmission in schools limited when strict mitigation measures used

Comments Off on SARS-CoV-2 transmission in schools limited when strict mitigation measures used

Paternal use of diabetes drug associated with genital birth defects in boys

Comments Off on Paternal use of diabetes drug associated with genital birth defects in boys

Changes in white matter connections during development linked to psychosis risk

Comments Off on Changes in white matter connections during development linked to psychosis risk

Researchers show the feasibility of a comprehensive sequencing approach in pediatric and young adult cancers

Comments Off on Researchers show the feasibility of a comprehensive sequencing approach in pediatric and young adult cancers

Create Account



Log In Your Account