Jessie Yanxiang Guo, an associate professor in the Department of Medicine at Robert Wood Johnson Medical School, was recently presented the Lung Cancer Discovery Award by the American Lung Association (ALA) Research Institute for her study on the link between the ketogenic diet and cancer metabolism, according to a press release.
The ALA gives the Lung Cancer Discovery Award to research considered promising in gaining a significant understanding of lung cancer, especially in populations who do not smoke. The award is a $100,000 grant with the opportunity to be renewed for an additional year.
Guo, a resident member at Rutgers Cancer Institute of New Jersey, said she has researched KRAS-driven lung cancer cell growth for eight years through genetically engineered rodent models.
KRAS is just one example of a cell growth mutation that appears in certain types of lung cancer and is associated with worse reactions to typical cancer treatment methods, according to the press release. Thus, dietary practices such as the ketogenic diet, which involves shifting fuel sources from carbohydrates to fats, can be used as treatments.
Guo said researchers want to know how diets skew energy balance in the already altered cancer cells. The idea came about when a previous graduate student in her lab suggested exploring the ketogenic diet in mice, according to Guo.
Currently, a ketogenic diet serves as a potential candidate to supplement multiple cancer treatments and inhibit PI3K, an enzyme that promotes cell growth, Guo said. The mechanisms of how this diet alters metabolism are unknown in the context of lung cancer, she added.
"How can we combine ketogenic diet with other therapy, like the PI3K inhibitor (that) has been proposed for pancreas cancer?" Guo said. "That is the main purpose for this grant."
Guo said that human clinical trials for the ketogenic diet falter due to individual discrepancies and failure to adhere to the diet. Therefore, mice become better model organisms to study how the new diet can enhance or diminish cancer growth.
The challenge with mice is motivating them to eat, Guo said.
Guo added that before-clinical-trial mouse models are vital for research. Most scientists progress from using cell culture in Petri dishes to agar, a substance used to grow microorganisms, to organs — but those studies cannot replicate the environment for tumor growth in organisms, she said.
If successful in overcoming those hurdles, findings from mice studies have the potential to translate to clinical trials, Guo said.
Mice studies consist of diet interventions across the tumor’s growth timeline, a combination of diet and other treatments to assess survival rate, as well as an evaluation of the number of genetic mutations in cancerous cells, Guo said.
She explained that tumor progression is measured through Micro-CT, an imaging method, and through monitoring cell death and cell growth.
With the grant, Guo said she hopes to develop an improved mouse model that is more responsive to cancer treatments and explain the biochemical mechanisms underlying the formation of lung tumors. The lab also looks forward to applying for the National Institute of Health's R01 grant once it gathers initial data, she said.
Guo said that current gene treatments for mutated DNA are not sufficient to target cancerous cells. For example, some mutations can be targeted, but for others, inhibitors have yet to be developed, according to her.
Therefore, she said ketogenic diet research explores how to improve cancer outcomes when joined with other treatments such as chemotherapy.
"These two years, we can have the general preliminary data and have publications but meanwhile expand more to really get deeper," Guo said.