Dr. Luke Hoeppner, head of the Cancer Biology lab at The Hormel Institute, has published new lung cancer research, shedding light on a protein that causes small cell lung cancer tumors to aggressively grow. The discovery is a breakthrough because now a specific target is known where intervening therapies could be developed. 

The research article, “ASCL1-regulated DARPP-32 and t-DARPP stimulate small cell lung cancer growth and neuroendocrine tumor cell proliferation” by Dr. Hoeppner and his team was published in the British Journal of Cancer, an impactful and highly cited general cancer journal. The scientific journal publishes significant advances in basic, translational, and clinical cancer research. British Journal of Cancer is a Nature journal owned by Cancer Research UK, the world’s leading independent cancer charity, dedicated to saving lives through research. 

Dr. Hoeppner and his research team are dedicated to making basic science discoveries that will likely lead to new therapies, or ‘emergency brakes’, to permanently kill tumor cells and stop uncontrolled cancer cell growth. 

To help meet the urgent need for improved small cell lung cancer therapies, the Institute team of researchers used models and cancer patient-derived data to discover how small cell lung cancer cells to grow rapidly and without control. They showed for the first time that a protein called DARPP-32 plays an important role in promoting small cell lung cancer growth. They found that an established driver of tumor growth signals for greater production of DARPP-32, which in turn, activates other molecular players that stimulate cancer growth. Returning to the ‘car racing out of control’ analogy, their study suggests that DARPP-32 is essentially ‘pushing down the gas pedal’ to accelerate cancer growth. 

Lung cancer is the deadliest form of cancer among men and women in the U.S. and worldwide. Small cell lung cancer is a particularly deadly and aggressive type that accounts for about 15% of lung cancer cases. Chemotherapy is an effective treatment initially. Unfortunately, after about one year, small cell lung cancer progresses, despite chemotherapy, and little can be done to treat it. New approaches to prevent small cell lung cancer progression and therapy resistance will translate to better treatments and cures. 

This project was led by Dr. Sk. Kayum Alam, a senior postdoctoral fellow in Dr. Hoeppner’s lab who recently received a Fifth District Eagles Cancer Telethon Postdoctoral Fellowship Award to generously support his lung cancer research. Dr. Li Wang, a current postdoctoral trainee, and Christina Hernandez, a former Summer Undergraduate Research Experience (SURE) intern, both also from Dr. Hoeppner’s lab, made critical contributions to this innovative study. 

Dr. Rendong Yang, head of the Computational Cancer Genomics lab at The Hormel Institute, and Dr. Yanan Ren, a postdoctoral associate in Dr. Yang’s lab, used their bioinformatics expertise to computationally identify biological factors that control small cell lung cancer growth. Mayo Clinic collaborators, Dr. Anja Roden and Dr. Farhad Kosari, coordinated histological studies that suggest DARPP-32 proteins are overexpressed in patient- derived small cell lung cancer tissue, yet undetectable in normal lung specimens from healthy people.