A little dopamine could go a long way in treating lung cancer – Austin Daily Herald

Small cell lung cancer (SCLC), one of the deadliest types of lung cancer, is an aggressive tumor that metastasizes early compared to other cancers and can quickly develop resistance to chemotherapy  —  making it extremely difficult to treat.

However, at The Hormel Institute, University of Minnesota, scientists in the lab of Associate Professor Dr. Luke Hoeppner are working to change this  —  and one of the solutions might have something to do with activating dopamine receptors.

While dopamine is primarily known as a “feel-good” chemical that influences mood and motivation, its presence also influences a number of other bodily processes.

SCLC is initiated by neuroendocrine cells, and dopamine signaling regulates neuronal signaling. The Hoeppner Lab, through a study newly published in Cell Death & Disease, found that treating SCLC with a dopamine D2 receptor (D2R) agonist — a drug that activates the targeted dopamine receptors  —  was able to reduce the formation of new tumor blood vessels (a process called angiogenesis), stalling cancer progression. The D2R agonist used, called cabergoline, is already FDA-approved. Results from the study suggest it may also have potential for combatting chemotherapy resistance, making other treatments more effective.

“Activation of dopamine signaling reduces the tumor’s blood supply. We speculate that decreasing the vascular network of vessels surrounding the tumor increases the accessibility of chemotherapy drugs to the primary tumor, which explains why D2R agonist treatment sensitizes the SCLC to chemotherapeutic agents,” Hoeppner said.

While immunotherapies in recent years have helped to improve SCLC survival rates, only a small population of patients with late-stage SCLC respond significantly to immune checkpoint blockades, and reliable prognostic biomarkers to identify which patients will respond best don’t yet exist.

“Our work identifying new mechanisms of drug resistance and ways to combat chemotherapy-refractory SCLC progression may help develop new therapies to improve the clinical outcome of SCLC patients,” Hoeppner said.

Previously, the Hoeppner Lab discovered that activating dopamine signaling through the dopamine D2 receptor interrupts tumor progression and angiogenesis in non-small lung cell cancer. This led the researchers to investigate whether the same could also be true for SCLC.

The study was led by Dr. Sk. Kayum Alam, PhD, a former senior scientist in the Hoeppner Lab. Dr. Li Wang, PhD, researcher 5, and Dr. Anuradha Pandit, PhD, post-doctoral associate, of the Hoeppner Lab and Drs. Seyedeh Sahar Mortazavi Farsani, PhD, post-doctoral associate, and Vivek Verma, PhD, assistant professor, also made important contributions to this study and are listed as authors of the paper.

This study was supported by a Research Scholar Grant from the American Cancer Society, along with a recent additional $50,000 supplement from the American Cancer Society.