University of Illinois Cancer Center member Jiyeon Kim was selected to receive the Lung Cancer Discovery Award presented by the American Lung Association.
Kim’s research project, titled “Targeting hexosamine pathway in an aggressive subtype of lung cancer”, will focus on amino sugar and the nucleotide pathway.
“Cancer cells alter their metabolism by changing energy production and redox balance,” said Kim, PhD, assistant professor of biochemistry and molecular genetics. “Such alterations enhance survival and provide a selective advantage over normal cells during tumor proliferation. Given cancer cells’ dependence on these activities, altered metabolic pathways might be suitable targets for new drug development.”
In some human cancers, metabolic liabilities have been translated into effective therapies, Kim said. Inhibitors of dihydrofolate reductase – a small enzyme that plays a supporting, but essential role, in the building of DNA and other processes and manages the state of folate, a snaky organic molecule that shuttles carbon atoms to enzymes that need them in their reactions – have been used to treat various cancers, including lung, breast and lymphoma (drugs such as methotrexate, pemetrexed).
Alterations in metabolism usually results from mutations to genes that function as tumor suppressors or tumor promoters, Kim said. Her laboratory is conducting studies to understand how certain gene mutations alter metabolism in lung cancer, and how these changes create liabilities that can be exploited therapeutically.
“By integrating genetic and metabolic analyses, we discovered that the cellular content of glucosamine-related metabolites called hexosamines is dramatically increased by the combination of the two most common mutations in lung cancer,” Kim said. “In our study, we will dissect the role of these concurrent mutations in hexosamine metabolism and investigate strategies to inhibit hexosamine synthesis.”
Kim’s research will capitalize on a suite of mouse models of cancer, state-of-the-art techniques in metabolomics and metabolic flux analysis, and a novel technology permitting the editing of the cancer genome. If successful, “this work will have a major impact on cancer,” Kim said.
“First, it will provide guidelines to patients whether glucosamine restriction is beneficial. Secondly, it will evaluate the therapeutic importance of a metabolic vulnerability in a particularly aggressive subtype of lung cancer. I’m grateful to the American Lung Association for choosing me to receive this award, and I’m excited to begin the work.”
The Lung Cancer Discovery Award supports independent investigators conducting clinical, laboratory, epidemiological or any groundbreaking project aimed at revolutionizing the current understanding of lung cancer and improving diagnostic, clinical and treatment methods. The award is for $100K per year for up to two years.