Neuroblastoma is an unusual tumor disease of the nervous system that almost exclusively affects children, mainly younger than two years old. About half of the children have high-risk tumors with a lower chance of being cured. N-MYC is linked to poorer prognosis in neuroblastoma.

Most proteins have a definite three-dimensional structure that usually contributes to their function and how they interact with other proteins. MYC is different and does not really have a fixed three-dimensional structure. The protein is flexible and constantly changes shape, which poses a challenge to researchers seeking to understand how MYC proteins work.

Also, MYC proteins are involved in the processes necessary for healthy cells to grow and divide. To prevent all cells in the body being harmed, it is important that a drug inhibits only the MYC function that is the problem in cancer cells, and nothing else. In other words, it takes a molecule that specifically affects a certain interaction between N-MYC and another protein.

In the current study, the researchers focused on the protein Aurora A, which also has a role in neuroblastoma and many other tumor forms. Preventing these proteins from interacting with each other has been suggested as a way to treat childhood tumors.

“To stop an interaction, you need to know where it’s happening. Despite the fact that N-MYC constantly changes shape, we now know where the two proteins anchor to each other. This provided clues as to what the medication should look like. We’ve also found a small molecule that manages to break apart the proteins, which lays a good foundation for future clinical trials,” says the first author.

The authors show that N-Myc binding to the Aurora A N-lobe can be inhibited by the small-molecule AurkinA, providing opportunity for therapeutical strategies to disrupt this interaction. ScienceMission sciencenewshighlights.

Researchers show how two important cancer-related proteins can be prevented from collaborating with each other. The discovery shows the way towards future medications to combat e.g. neuroblastoma in children. Their study has been published in the journal Nature Communications.

“Today we can cure many cases of childhood cancer that were incurable ten years ago. But there’s still an important group of childhood tumors that evade cure. Researchers in this field are looking for ways to affect cancer cells when nothing else works,” says the senior author.

The research group has spent several years researching a protein family, called MYC proteins, that plays important roles in the development of many types of cancer. In the current study, they focused on N-MYC. N stands for neuroblastoma, the cancer form in which the protein was first discovered.