INNOVATIVE RESEARCH: DEVELOPING NEW PANCREATIC CANCER THERAPIES

Zinc transporter: ZIP4

Story by Elisabeth Slay Archived photo

Those in the Research Division of the University of Oklahoma Department of Surgery study various types of cancer According to researcher and professor Dr Min Li, his team is dedicated to studying pancreatic cancer pathogenesis and the development of new therapies to treat patients.

“Our research covers early detection, molecular mechanism, and targeted therapy of pancreatic cancer,” he said “Current projects in the laboratory include the role of zinc transporter ZIP4 in pancreatic cancer progression, the therapeutic potential for ZIP4 shRNA, the function of microRNAs in ZIP4-mediated tumor growth, signaling transduction and metabolism in pancreatic cancer, and cancer cachexia “

Dr. Li explained his group is the first to identify a key zinc transporter called ZIP4 which is “aberrantly expressed in pancreatic cancer, and promotes tumor growth, epithelial-mesenchymal transition (EMT), and metastasis, suggesting that ZIP4 serves as a novel prognostic and predictive marker for pancreatic cancer." The researcher has conducted various research projects through the years and his team’s most recent findings suggest ZIP4 promotes muscle wasting and cancer cachexia

"Also known as rapid conditioning, Dr Li said cachexia is a dysfunction in the body that causes uncontrollable weight loss independent of nutritional supplements

“Muscle wasting, adipose loss, and loss of appetite (anorexia) are prevalent in those patients. Cachexia is associated with multi-organ dysfunction and increased mortality,” he said “Currently, no effective treatment options have been approved to reverse or ameliorate cancer cachexia Novel therapeutic targets and treatmen strategies are urgently needed ”

Dr. Li explained pancreatic cancer has the highest prevalence of cachexia more than any other form of cancer. “Our recent study, Acetyl-Coenzyme A Synthetase 2 Potentiates Macropinocytosis and Muscle Wasting Through Metabolic Reprogramming in Pancreatic Cancer found that metabolic stress can induce ACSS2 expression

Furthermore, ACSS2 promotes muscle wasting through GSK3β/TRAIL axis, resulting in muscle wasting, which potentially provides nutrients to maintain tumor fitness,” he said. “ACSS2 dominates the metabolic reprogramming by orchestrating macropinocytosis and muscle wasting to support tumor progression in pancreatic cancer ”

The medical professional said targeting ACSS2 would help prevent the development of cachexia in pancreatic cancer patients “This study expanded our knowledge on the complex mechanism of cancer cell macropinocytosis under metabolic stress conditions and the release of tumor-derived factors stimulating muscle wasting in pancreatic cancer,” he stated.

Dr Li is inspired to study pancreatic cancer as it is a catchment area of the Stephenson Cancer Center and it’s one of the most fatal forms of cancer “Innovative research focusing on pancreatic cancer such as new mechanisms, and new therapies are timely and urgently needed. I am excited to take this opportunity to pursue this innovative research in pancreatic cancer,” he said.

It’s the change innovation brings that Dr Li enjoys most about conducting his research “I hope this research will lead to a better understanding of the biology of pancreatic cancer, and help to develop a new therapy for this terrible disease,” he said In recent years, Dr Li’s team has published various studies with their findings and new therapies.

“Our studies indicate that ZIP4-based therapy can sensitize the pancreatic cancer cells to chemotherapy; therefore, a combinational therapy using ZIP4 shRNA and chemotherapy may further increase the efficacy of individual treatment for pancreatic cancer,” he said.

“Our studies also elucidated the complex mechanism of cancer cell macropinocytosis under metabolic stress conditions and the release of tumor-derived factors stimulating muscle wasting and cancer cachexia in pancreatic cancer Furthermore, our recent study indicated that a combination of local phototherapy and immunotherapy induced systemic immunity against established tumors and metastases in an aggressive, preclinical pancreatic tumor model, leading to a potential clinical method for patients with advanced pancreatic cancer ”

The researcher explained several colleagues are involved with these studies including Drs Barish Edil, Ajay Jain, and Lacey McNally “This creates multidisciplinary collaborations, and training opportunities for our junior faculty, residents, and fellows,” he said. “More importantly, it will benefit the patients diagnosed with pancreatic cancer and improve the overall clinical and research programs in the Department of Surgery “

Going forward Dr Li hopes to identify new “diagnostic and therapeutic markers in pancreatic cancer which can be translated into new clinical trials and benefit patient care at OUHSC.

The medical profession is grateful to the department and Chair of the Department Dr. Edil for creating an environment that’s supportive of growth