What’s New in Neuroblastoma Research?

Important research into neuroblastoma is being done right now in many university hospitals, medical centers, and other research institutions around the world. Each year, scientists find out more about what causes the disease and how to improve treatment.

Genetics of neuroblastomas

Researchers now have better tests to look for changes in the genes of neuroblastoma cells. Researchers might know that a change has happened on a certain chromosome (a strand of DNA inside the cell, which contains its genes), but they still need to know more about that gene or what part of a gene has been affected. There are a few different ways that genes change in neuroblastoma:

  • Sometimes there are extra copies of the same gene (called amplification) on a chromosome.
  • Sometimes a chromosome can have missing pieces of DNA (called deletions) or extra pieces of DNA (called gains or additions), which can affect which genes the chromosome has.

Understanding the gene changes in neuroblastoma helps researchers understand which neuroblastomas are likely to be cured with less intense treatment, and which will need more aggressive treatment. More aggressive neuroblastoma tumors are often called high-risk neuroblastomas, while tumors that tend to be easier to treat are called low- or intermediate-risk neuroblastomas. Some of these gene changes are being used now to help cancer care teams determine a child's neuroblastoma stage and risk group. Other gene changes might help researchers find new treatments that work on certain types of neuroblastoma cells.

Here are some specific DNA and gene changes currently being studied:

  • DNA changes on the short arm of chromosome 6 (6p22) are more likely to be seen in neuroblastomas that grow more aggressively.
  • Neuroblastoma cells in older children are more likely to have changes in the ATRX tumor suppressor gene. Tumors with this gene change tend to grow more slowly, but they are also harder to cure. This may help explain why older children tend to have high-risk neuroblastoma while younger children tend to have low- or intermediate-risk neuroblastoma and do better.
  • Changes in or having more than one copy (amplification) of the ALK and MYCN genes are features used to help decide a child's risk group. Some drugs might work well against neuroblastomas with ALK gene changes. Some scientists also are studying how ALK gene changes might be related to extra copies of the MYCN gene in neuroblastoma cells.


Survival rates for neuroblastoma have gotten better as doctors have found ways to improve on current treatments, but survival rates for children with high-risk neuroblastoma are not as good as they are for children with low- or intermediate-risk disease. Most research studies about high-risk neuroblastoma (more aggressive and hard to treat tumors) focus on finding the best combinations of chemotherapy drugs, stem cell transplant regimens, immunotherapies and other new treatments to try to cure more children. Current studies of low- and intermediate-risk neuroblastoma are trying to figure out if children can get less treatment and still do as well.


The search continues for the best combinations of chemotherapy drugs to treat neuroblastoma.

Several chemotherapy drugs that are already used to treat other cancers, such as topotecan, irinotecan, and temozolomide, are now being studied in combination with other kinds of therapies for use against high-risk neuroblastoma or neuroblastoma that has come back.

Other studies are looking to see if children with low- or intermediate-risk neuroblastoma can be treated with less (or even no) chemotherapy. The goal is to still have the same good results, but with fewer side effects from treatment.

Stem cell transplants

Doctors are also trying to improve the success rate for children with aggressive neuroblastoma with high-dose chemotherapy and stem cell transplants, using different combinations of chemotherapy, radiation therapy, retinoids, and other treatments. A recent clinical trial looked at whether giving two stem cell transplants to children with high-risk neuroblastoma works better than giving just one stem cell transplant. The long-term improvement in survival for children who received two transplants is not yet clear, but early results show that two stem cell transplants, followed by certain kinds of immunotherapy works better than one stem cell transplant . Other studies are looking to see if using stem cells donated from another person (an allogeneic stem cell transplant) might help some children with hard-to-treat tumors. More research will be done to confirm these results. If you have questions about this, talk with your doctor.


Retinoids such as 13-cis-retinoic acid (isotretinoin) have reduced the risk of recurrence after treatment in children with high-risk neuroblastoma, especially when they are given with certain immunotherapy treatments. Giving 13-cis-retinoic acid in combination with different types of chemotherapy drugs, immunotherapies called monoclonal antibodies, and targeted drugs is being studied in a number of clinical trials to help determine the combinations that might work the best.
Targeted drugs

Knowing what makes neuroblastoma cells different from normal cells could lead to new approaches to treating this disease. Newer drugs that target neuroblastoma cells more specifically than standard chemo drugs are now being studied in clinical trials. For example, doctors are now studying medicines that target the pathways inside neuroblastoma cells that help them grow, such as crizotinib (Xalkori) for the ALK pathway and alisertib (MLN8237) for the aurora A pathway.

Crizotinib is a drug that targets cells with changes in the ALK gene. Up to 15% of neuroblastomas have changes in this gene. In an early study, crizotinib was found to cause some neuroblastomas to shrink, although it’s not clear how long this might last, or if giving this drug with certain chemotherapy drugs might work better. Other drugs that target cells with ALK changes are being developed. Some of these are approved for treating other cancers and are being studied to see if they work in neuroblastoma.

Some other drugs that work differently from standard chemo drugs are being studied in clinical trials against neuroblastoma as well. Examples include bortezomib, vorinostat,, temsirolimus, bevacizumab, nifurtimox, and DMFO.


Immunotherapy is the use of medicines to help a patient’s own immune system fight cancer. A few different kinds of immunotherapy are being used in neuroblastoma.

Anti-GD2 monoclonal antibodies

The monoclonal antibody dinutuximab (Unituxin®), which targets GD2 on neuroblastoma cells, is now used routinely for children with high-risk neuroblastoma, to help immune system cells find and destroy the cancer cells.

Clinical trials are now testing the effectiveness of several other antibodies that target GD2:

Hu14.18-IL2 is an antibody that is linked to interleukin-2 (an immune-boosting cytokine). Early results have found that this antibody/cytokine combination may help some children for whom other treatments are no longer working.
Hu14.18K322A is a modified antibody that might work as well as other GD2 antibodies without some of the side effects.
Hu3F8 is another modified antibody that targets GD2. It is being studied in combination with other treatments.


Several cancer vaccines are also being studied for use against neuroblastoma. For these vaccines, injections of modified neuroblastoma cells or other substances are given to try to get the child’s own immune system to attack cancer cells. These treatments are still in the early stages of clinical trials.

CAR T-cell therapies

CAR T-cell therapy is a promising new way to get a patient's own immune cells called T cells (a type of white blood cell) to fight cancer by changing them in the lab so they can find and destroy cancer cells. The T cells used in CAR T-cell therapies get changed in the lab to spot specific cancer cells by adding a man-made receptor (called a chimeric antigen receptor or CAR). One early trial created CAR T-cells to target GD2 on neuroblastoma cells. Other clinical trials are studying using CAR T-cells that target other proteins on the outside of neuroblastoma cells. These are very new clinical trials and are ongoing or in the planning phase. Talk to your doctor about these trials if you have questions.

This information is reproduced with permission of The American Cancer Society from their page: What's New in Neuroblastoma Research.

The American Cancer Society medical and editorial content team is made up of doctors and oncology certified nurses with deep knowledge of cancer care as well as journalists, editors, and translators with extensive experience in medical writing.

Last Medical Review: March 19, 2018 Last Revised: March 19, 2018