Breakthrough made in lung cancer research

Published 7:01 am Saturday, June 13, 2020

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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.

Dr. Luke Hoeppner

The research article, “ASCL1-regulated DARPP-32 and t-DARPP stimulate small cell lung cancer growth and neuroendocrine tumor cell proliferation” by Hoeppner and his team was published in the British Journal of Cancer, an impactful and highly cited general cancer journal.

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“In the human body, balanced cell growth and death help a person stay healthy. In adults, as many as one trillion cells die each day to be replaced by other cells,” said Hoeppner. “Unfortunately, cancer occurs when cells acquire aggressive characteristics and grow uncontrollably – imagine a car racing down I-90 with the accelerator pedal stuck to the floor with brakes that do not work, as an analogy of unchecked cellular growth that causes tumors.”

Hoeppner and his research team are making basic science discoveries that will likely lead to new therapies to permanently kill tumor cells and stop uncontrolled cancer cell growth.

To help meet the 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 and 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.

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 percent 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.

“To build on our basic science discovery, we will seek support to translate our findings into methods to prevent, diagnose, or treat small cell lung cancer progression,” Hoeppner said. “Our ultimate goal is to improve the lives of individuals afflicted with this devastating disease locally, nationally, and beyond.”

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

“Team science is one of the keys to success in cancer research,” Hoeppner said. “I value and am proud of important partnerships with experts throughout Minnesota.”