A team of researchers at VCU Massey Comprehensive Cancer Center has been awarded a $13 million grant from the National Cancer Institute (NCI) to investigate new treatment strategies for liver cancer, the third-leading cause of cancer-related deaths worldwide. The five-year P01 grant, the first of its kind awarded to Massey, will support four research projects focused on understanding the biology of liver tumors and developing effective drug combinations for hepatocellular carcinoma (HCC), the most common form of liver cancer.
Addressing Unmet Needs in Liver Cancer Treatment
Currently, treatment options for liver cancer, including combinations of immunotherapies and tyrosine kinase inhibitors (TKIs), offer limited long-term benefits. Clinical trials show that immunotherapy is effective in less than one-third of liver cancer patients, and nearly all patients treated with TKIs develop resistance within a year. According to Devanand Sarkar, M.B.B.S., Ph.D., principal investigator on the grant, patient survival rates with current treatments for advanced disease remain less than two years.
Targeting MYC and TAF2 in Liver Tumors
The research projects will explore the ability of a new drug, developed by collaborators at Northwestern University, that inhibits the function of MYC, a gene amplified in about one-fifth of all HCC patients. The studies will evaluate the MYC inhibitor in combination with existing immunotherapies.
One project, led by Arun Sanyal, M.D., and Huiping Zhou, Ph.D., will focus on obesity-associated liver cancer, specifically metabolic dysfunction-associated steatohepatitis (MASH)-driven HCC. They will evaluate the MYC inhibitor in combination with other drugs in this context, given the role of MYC in regulating MASH-associated HCC.
Sarkar's project will investigate the role of TAF2, a gene found to partner with MYC to fuel cancer growth. The initiative will attempt to block both TAF2 and MYC in liver tumors using a combination of targeted drugs and immunotherapies.
Novel Antibody and Fusion Cytokine Approaches
Shawn Wang, Ph.D., will investigate the MYC inhibitor in combination with an antibody he previously developed against scavenger receptors in myeloid cells.
Paul B. Fisher, M.Ph., Ph.D., FNAI, will lead an immune-focused effort to combine the MYC inhibitor with a fusion cytokine, an engineered biopharmaceutical that targets and kills cancer cells while eliciting a targeted immune response against the tumor.
Collaborative Synergy for Clinical Translation
The long-term goal of the grant is to translate findings from at least one, if not all, of these projects into a clinical trial. According to Sarkar, the collaborative effort is expected to be more synergistic than individual lab work, allowing the team to ask questions that have not been asked before. Aliasger Salem, Ph.D., of the University of Iowa and Alexander Kilbanov, Ph.D., of UVA Cancer Center will also collaborate on this grant-funded initiative.
