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Luke Hoeppner, PhD, associate professor at The Hormel Institute, University of Minnesota, is the recipient of a $50,000 supplemental award from the American Cancer Society (ACS). 

The award will support small cell lung cancer research connected to Hoeppner lab’s currently funded ACS Research Scholar Grant of more than $780,000 that was awarded for a four-year period beginning in 2021. The research has the potential to pave the way for new treatment options for small cell lung cancer, one of the deadliest lung cancer subtypes. 

Lung cancer is the leading cause of cancer death in the United States, and small cell lung cancer (SCLC) is the most aggressive form of lung cancer, with only about 7% of patients surviving more than five years. SCLC accounts for about 15% of lung cancer cases in the United States. In small cell lung cancer, it has proven difficult to target specific mutations during 

a patient’s treatment, because many different types of mutations can occur. 

“Standard therapy for SCLC patients has not substantially improved since the introduction of chemotherapeutic agents over 30 years ago because oncogenic drivers remain poorly understood,” Hoeppner said. “Recent advances in immunotherapy have proven effective against some types of SCLC, but immunotherapy is not effective in many cases of SCLC. New strategies to treat small cell lung cancer are urgently needed.” 

This supplemental award from the ACS will support the search for new, originally unanticipated directions of research beyond what was originally proposed in the lab’s initial grant, but that still fall within its scope. 

Stimulating molecular signaling through the dopamine D2 receptor helps inhibit blood supply to tumors, which they need to grow and thrive. The lab is investigating whether molecular signaling through the receptor to cut off the blood supply to small cell lung cancers will transform the tumor microenvironment from immunosuppressive (weakening or stopping immune responses) to immunostimulatory (boosting or stimulating immune responses) by increasing the recruitment and activation of the immune system’s CD8+ T cells. 

Hoeppner and investigators at Mayo Clinic were the first to report that activation of dopamine signaling pathways reduce other forms of lung cancer growth. The Hoeppner lab has demonstrated that several genes in the dopamine pathway promote drug resistance in lung cancer, as was previously shown by others to be the case with breast and gastric cancers. 

The ACS Research Scholar Grant initially awarded in 2021 supports the ongoing research investigating whether therapeutically altering the dopamine signaling pathway may be viable as a new approach to inhibit small cell lung cancer progression and drug resistance that will have the potential to pave the way for new strategies to treat small cell lung cancer and/or prevent resistance to current therapies. 

“Immunologist and The Hormel Institute Assistant Professor Vivek Verma, PhD, is a co-investigator as part of this supplemental award and has been invaluable in providing scientific and technical support. We couldn’t do these studies without Dr. Verma as a collaborator,” Hoeppner said. 

Postdoctoral Associate Anuradha Pandit, PhD, in Hoeppner’s group has been performing the studies supported by this supplemental support from ACS. Postdoctoral Associate Sahar Mortazavifarsani, PhD, in Dr. Verma’s research group, has also been instrumental in launching this project. 

Dr. Sk. Kayum Alam and Dr. Li Wang, senior researchers in Hoeppner’s group, have also made important contributions to the overall project. 

“We are well positioned to overcome these challenges thanks to several innovative tools and resources we possess, including SCLC specimens and in vivo models. We aim to challenge the current paradigms in human SCLC by discovering the underlying mechanisms of drug resistance to develop new therapies to improve the clinical outcome of people diagnosed with SCLC,” Hoeppner said.