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Young Investigator Seeks a Target for Targeted Neuroblastoma Therapy

Published on
Oct 20, 2015

It is scary to learn your child has neuroblastoma, a tumor of the peripheral nervous system that is the most common cancer in infants. It is scarier still when you get test results that show your child is in the half of neuroblastoma patients whose cancer is very aggressive and high-risk. Doctors routinely test neuroblastoma tumor genes to see if there are multiple extra copies of the gene MYCN. Positive results come with that high-risk prognosis. Amplified MYCN occurs in about half of all high-risk neuroblastoma cases.

Currently, there is not a good answer for parents facing this scenario. Doctors have known about the association between amplified MYCN and poor neuroblastoma outcomes for more than 30 years, but that knowledge has not yet translated into improved, targeted treatments.

One researcher who is now trying to make the start of that translation is Robyn Sussman, PhD, a postdoctoral fellow at The Children’s Hospital of Philadelphia. Dr. Sussman has just received a two-year Young Investigator grant from the Alex’s Lemonade Stand Foundation (ALSF) to pursue this line of research. This week, she is joining 50 researchers from across the country at the third ALSF Young Investigator Summit to learn from and engage with leading researchers in pediatric oncology.

In her preliminary research, Dr. Sussman has looked at genes in neuroblastoma tumors, comparing samples with low and high levels of MYCN expression. She searched for signs of what MYCN might be controlling, in hopes of finding something that would offer a vulnerable point to attack MYCN-amplified cancer cells.

“MYCN controls the expression of many genes,” Dr. Sussman said.

However, there is no publicly available list of genes that are directly controlled by MYCN, so Dr. Sussman is finding those genes and creating a list that she is preparing for publication.

In particular, within that list of MYCN-controlled genes, she looked for genes that might produce proteins exposed on the surface of the tumor cell’s membrane. A targeted therapy needs something that is exposed on the cancer cell’s surface to latch onto, so Dr. Sussman is particularly seeking a protein that is exposed on the surface on cancer cells but not healthy cells. Her lab specializes in developing targeted immunotherapies. If she does identify a cancer-specific surface protein, her team can follow up on that discovery by training the body’s immune system to attack this target.

Already, she has found one promising target called CAMKV. Little is known about the CAMKV protein, though, other than that it is concentrated in neuroblastoma tumors that have amplified MYCN. Dr. Sussman’s next step is to try to hunt for signs that some portion of the CAMKV protein sticks out from the cell’s plasma membrane — to find that target for a targeted therapy that can help patients with these aggressive cases of neuroblastoma.

If CAMKV does not fit the bill, then the search will continue. Dr. Sussman’s list of MYCN-controlled genes has other promising candidates.

“What’s most important and exciting about this is that any therapy that comes out of this work would have a clinical biomarker already in place,” Dr. Sussman said, because neuroblastoma patients are already routinely tested for amplified MYCN. “We would not have to develop a new test to see who would be eligible for the therapy.”

The list of MYCN-controlled genes Dr. Sussman is generating from MYCN-amplified neuroblastoma cells also holds promise to help other researchers pursue their own avenues of study. MYCN is one of the most-studied genes in neuroblastoma research, and it is similar to c-MYC, one of the most common oncogenes in other cancers.

“Once these data are publicly available in public databases, it’s going to be an incredible service to everyone else studying MYCN,” Dr. Sussman said.