Page 33 - The Hormel Institute 2024 Annual Report

Lung cancer is the leading cause of cancer death in the United States and worldwide. Small cell lung cancer (SCLC) is the most
aggressive form of lung cancer. We are currently studying the role of dopamine signaling in SCLC initiation, progression, and acquired resistance to chemotherapy. This research is supported
by a four-year Research Scholar Grant from the American Cancer Society.
We recently received a supplemental award from the American Cancer Society to support new, originally unanticipated directions of research beyond that originally proposed in the lab’s initial grant, but that still fall within its scope. The new research supported by the supplemental grant
is focused on investigating whether activation of dopamine signaling helps make small cell lung cancer more susceptible to immunotherapy.
Collectively, our lab’s ACS Research Scholar Grant and its new supplemental award support ongoing research determining how therapeuti- cally altering the dopamine signaling pathway may be viable as a new approach to inhibit small cell lung cancer progression and drug resistance. This research has the potential to pave the way for new strategies to treat small cell lung cancer and prevent resistance to current therapies.
We are also investigating two new mechanisms of resistance to targeted therapies in non-small cell lung cancer (NSCLC).
1First, we are testing predictive biomarkers of acquired resistance and aiming to dis- cover new ways to prevent EGFR (epider-
mal growth factor receptor) inhibitor refractory lung cancer progression in work currently fund- ed by the Lung Cancer Research Foundation and EGFR Resisters. We demonstrated that a protein called IKKα drives NSCLC growth through activa- tion of oncogenic signaling via DARPP-32-medi- ated inhibition of protein phosphatase 1 activity (NPJ Precision Oncology, 2023).
2Secondly, in newly conceived studies supported by a community-funded Paint the Town Pink pilot project grant, our
group has shown that increased cilia formation in lung cancer cells is linked to the development of resistance to therapy. Cilia are microtubule- based sensory organelles that detect extracel- lular stimuli. We are actively researching how these new mechanisms of resistance can be manipulated to prevent the development of therapy-refractory lung cancer progression.
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