VCU news

By John Wallace
VCU School of Dentistry

Anthony Faber, Ph.D., a professor in the Philips Institute for Oral Health Research at the Virginia Commonwealth University School of Dentistry and Massey Comprehensive Cancer Center, is being awarded four grants totaling more than $6.3 million to aid in the development of new targeted therapies for neuroblastoma and synovial sarcoma, two rare cancers primarily affecting children and young adults.

Three of the grants are Research Project Grants (R01s) to be awarded by the National Cancer Institute, with two of the research projects focusing on neuroblastoma and the other on synovial sarcoma. The fourth grant is a smaller award from the Department of Defense that complements the NCI-funded synovial sarcoma research.

Neuroblastoma is a type of cancer that develops in nerve tissue, most commonly in the glands around the kidneys. While some progress has been made in recent years, high-risk neuroblastoma is responsible for the most cancer-related deaths in children 5 years and younger. Synovial sarcoma is another rare cancer that affects young adults. It tends to occur near major joints, such as the knee, and often spreads into other regions of the body. The 15-year survival rate for metastatic synovial sarcoma is less than 50%.

“The cancers that we’re studying in these grants are driven by transcriptional modifiers,” said Faber, who is also the Natalie N. and John R. Congdon, Sr. Endowed Chair in Cancer Research at Massey. “These cancers don’t have targeted therapy options because it is difficult to develop drugs that target transcriptional modifiers. However, we believe that we have uncovered biological processes that could lead to new therapies complementing current standards of care.”

When cells replicate, a process of transcription takes place where a segment of DNA, which contains the information needed for cellular replication, is copied into RNA. The proteins that help monitor and control this process are known as transcriptional modifiers. In cancer, these proteins are often erroneously altered, leading to the development of cancer.

In these projects, Faber and his team are focusing on the activity of two transcriptional modifiers, a fusion protein known as SS18-SSX that is found exclusively in synovial sarcoma, and one found in high-risk neuroblastoma, called MYCN.

One of the NCI-funded grants focuses on MYCN-amplified neuroblastoma, a more lethal subtype in which the MYCN protein is expressed at much higher levels than typically observed. The researchers will be testing the effectiveness of a class of drugs known as ferroptosis inducers. Ferroptosis is a form of programmed cell death discovered fairly recently that is misregulated in several tumors.

The three other grants are testing a new type of drug known as a SUMOylation inhibitor, with one project testing them against MYCN-amplified neuroblastoma and the others focusing on synovial sarcoma. Through a process of genetic screening, the team found these two cancers were both uniquely sensitive to this class of drug. Now, Faber’s team will attempt to discover why.

“I’m very excited by the teams that we have assembled to take on these projects – we have a number of external collaborators from universities across the world whose expertise integrate well with the strengths we have here at VCU. Ultimately, we want to offer new hope to patients suffering from these cancers,” Faber said. “We believe these treatment approaches could complement existing therapies such as chemotherapy and radiation, and, based on our results, we are already discussing plans with Dr. Poklepovic, the associate director of clinical research at Massey, to move this drug into clinical trials.”

“These grants show the strength of our research here at the Philips Institute and why VCU is at the forefront of science in terms of dental schools,” said Iain Morgan, Ph.D., associate dean for research at VCU School of Dentistry.

VCU School of Dentistry is currently ranked 17th among all dental schools in terms of National Institutes of Health funding, and these four grants provide a significant increase to the school’s research funding.

“Biomedical research is extremely expensive. We talk about food inflation and energy inflation, but there’s been biomedical research inflation going on for years and years,” Faber said. “These big grants are really essential to be able to do any of these experiments and to push this research forward.”