Massey researcher awarded $5.4 million to investigate novel therapies for liver cancer
Researchers at VCU Massey Cancer Center were awarded $5.4 million in grant funding from the National Cancer Institute (NCI) to investigate the potential for novel therapies to treat hepatocellular carcinoma, the most common type of liver cancer.
Hepatocellular carcinoma (HCC) is the fifth most prevalent cancer overall and is the second leading cause of cancer deaths worldwide. HCC’s lethality is largely due to the fact that there is not a successful therapy to treat the disease in advanced stages.
Devanand Sarkar, Ph.D., associate director for education and training, Harrison Foundation Distinguished Professorship in Cancer Research and member of the Cancer Molecular Genetics research program at Massey, received two R01 grants to identify key genetic players that regulate HCC and translate that knowledge into effective targeted therapies. R01 grants are highly competitive and provide funding for research and development supporting the missions of the National Institutes of Health.
The first grant, worth $2.4 million over the course of five years, will focus on the roles of two interacting proteins, AEG-1 and SND1. Previous research conducted by Sarkar has significantly implicated both genes in the development of HCC; however, it remains unclear what biological functions drive the cooperation between them to fuel tumor growth.
“Through our studies, we hope to achieve an in-depth understanding of the molecular mechanisms by which AEG-1 and SND1 promote HCC and evaluate a combination of drugs to inhibit both proteins in a mouse model,” Sarkar said. “If successful, we will have preclinical evidence supporting the development of new therapies targeting these genes.”
The second grant awarded to Sarkar, totaling $3 million over five years, will examine the antitumor properties of a specific protein, insulin-like growth factor binding protein-7 (IGFBP7), and determine its efficacy in targeted treatments for HCC. Xiang-Yang Wang, Ph.D., Mary Anderson Harrison Distinguished Professorship in Cancer Research and member of the Cancer Molecular Genetics research program at Massey, will serve as a multi-PI on this grant.
Many cancer cells are able to evade detection by the immune system and are important to the facilitation of tumor growth. Identifying the genetic regulators of anti-tumor immunity can help to exploit those evasive properties and contribute to the development of therapeutic strategies.
IGFBP7 has been shown to inhibit a key cellular signaling pathway that suppresses anti-tumor response in HCC and stifles tumor growth. Sarkar’s previous research findings strongly suggest that IGFBP7 plays a critical role in regulating the tumor microenvironment and anti-tumor immune response in HCC.
He hypothesizes that therapeutic administration of IGFBP7 will not only inhibit cancer cell survival but also enhance immune recognition of tumors.
“This would result in more effective eradication of tumors and metastases and potentially help save the lives of many HCC patients for whom an effective drug does not exist,” said Sarkar, also a professor of human and molecular genetics at the VCU School of Medicine.
To complete this research, Sarkar will perform in-depth molecular, biochemical, immunological and therapeutic studies in mouse models.
Co-investigators on Sarkar’s research into the AEG-1 and SND1 genes include Mikhail Dozmorov, Ph.D., member of the Cancer Molecular Genetics research program at Massey; Shah Giashuddin, M.D., of the NY Presbyterian Brooklyn Methodist Hospital; and Aliasger Salem, Ph.D., of the University of Iowa. Dozmorov and Salem are also co-investigators on the IGFBP7 research.