Liver cancer is the third-leading cause of cancer-related deaths worldwide, and the disease is often diagnosed at an advanced stage when there are significantly limited treatment options. A group of highly experienced researchers at VCU Massey Comprehensive Cancer Center was awarded more than $13 million through a team science grant from the National Cancer Institute to collectively unearth new, effective drug combinations for this largely untreatable cancer.
The five-year grant – the first P01 grant ever awarded to Massey in its five-decade history – will initiate a four-pronged approach to better understand the biology of liver tumors and advanced treatment options for hepatocellular carcinoma (HCC), the most common form of liver cancer.
"There are no other large, grant-funded projects like this in the country for obesity-associated liver cancer; it has the potential to change the way the disease is treated," said Devanand Sarkar, M.B.B.S., Ph.D., the principal investigator on the grant, as well as associate director of cancer research training and education coordination and member of the Cancer Biology research program at Massey. "Within the umbrella of this grant, we have four separate research projects asking different molecular questions, but with the same ultimate goal of identifying how we can exploit our findings to improve the efficacy of immunotherapy in liver cancer."
When diagnosed early, liver tumors are generally small and can be removed surgically or a liver transplant can be successfully performed. However, liver cancer is usually diagnosed when the tumor is much larger in size, the disease has spread to other organs and other associated health problems have already occurred.
Currently, there are a few available treatment options for liver cancer, including a combination of immunotherapies and a class of drugs known as tyrosine kinase inhibitors (TKIs), but their long-term effects are limited.
"Clinical trials show that immunotherapy is effective in less than one-third of liver cancer patients, and nearly 100% of patients who are treated with TKIs invariably develop resistance to the drugs within one year," said Sarkar, who holds the Harrison Foundation Distinguished Professorship in Cancer Research at Massey and has been studying HCC throughout his entire career. "Even with the current treatments that are available for advanced disease, the patient survival rates are roughly less than two years."
Previously, Sarkar has extensively studied MYC -; a gene that operates individually to drive tumors and is amplified in about one-fifth of all HCC patients -; as well as other genes that cooperate with MYC to accelerate liver cancer growth.
Through four different research projects, this grant will enable the investigators to explore the ability of a new drug, developed by collaborators at Northwestern University that inhibits the function of MYC, to effectively thwart liver cancer in combination with existing immunotherapies:
The long-term goal is to move findings from at least one, if not all, of these projects forward into a clinical trial.
"Our collective energy is a lot more synergistic than what we have all been doing individually in our own labs," Sarkar said, adding that this group of scientists boasts more than 300 published research papers combined. "With this grant, we are asking questions that have not been asked before."