The award recognizes one paper annually with “the potential to shift paradigms, inspire translational activity, and raise awareness of new scientific areas.” Madak Erdogan was honored as the corresponding author for this highly collaborative paper, “Targeting Metabolic Adaptations in the Breast Cancer-Liver Metastatic Niche Using Dietary Approaches to Improve Endocrine Therapy Efficacy,” published in June 2022.
“The award is an encouragement to pursue more studies like this one. We had to work hard initially to prove that our system was an adequate representation of liver metastasis for breast cancer patients. There was skepticism. Science is always a process, though,” said Madak Erdogan. 
“At the time of our paper’s publishing, our system was a novel and disputed concept, but as the paper was shared, cited, and tested, our system is now more mainstream in the lab and the field.”
Madak Erdogan's system includes a hydrogel-based system to characterize how tumor cells behave in the liver microenvironment. Through a diverse collaboration that included CCIL members David Shapiro and Benita Katzenellenbogen and external partners MD Anderson and Xylyx Bio using 3D models, mouse models, and in vivo and in vitro studies, the team developed a novel hydrogel system that allowed them to study the effects of a fasting-mimicking diet (FMD) upon endocrine therapies in metastatic liver tumors.
“Liver metastatic tumors are known to be difficult to manage for estrogen receptor-positive breast cancer patients. Treatments have not been effective. Our lab wanted to understand this phenomenon better and explore solutions to increase the efficacy of endocrine treatments upon the metastatic tumors,” said Madak Erdogan.
Using a combination of RNA and ChIP sequencing and metabolomics to analyze molecular changes in cancer cells grown in novel hydrogels, her team found that the activity of metabolic pathways relying upon glucose increased. Combining this knowledge with the understanding that FMD reduces glucose metabolism, her team used FMD in models to determine if the liver tumors would present less resistance to the treatment. And that is indeed what happened. The synergistic effect of the diet and the treatment presented promising results.
“When you have a drug that targets a particular pathway, you almost always have a side effect. And invariably, cancer finds a way to overcome the effects of a single chemical. You are dealing with millions of cells, and it only takes one or two mutations for the cancer to keep growing. With FMD, there are a multitude of effects on the body’s overall system, not just on the cancer cells. So, on the liver, a tumor has direct access to every nutrient from the intestine. FMD changes liver physiology itself. We showed that tumors find ways to hijack a critical system that stores energy in the form of glycogen. Instead of liver cells, tumors hoard the glucose and store its energy. With the incorporation of FMD, the tumor was depleted of immediate energy sources. So, FMD can starve the tumor while the therapy is administered, facilitating less treatment resistance,” explained Madak Erdogan.
“We are delighted and honored that AACR has selected Madak Erdogan’s work for its significance and timeliness,” said CCIL Director Rohit Bhargava. 
“Characteristic of Zeynep’s work, this study is not only of high scientific quality but can potentially change our thinking and inspire translational activity.”
Madak Erdogan’s team is working on a follow-up paper to expand this research and anticipates future clinical studies.

Article published in Cancer Center at Illinois Innovation Insider newsletter- Spring 2024