Inhibition of Neural Signaling Pathways in Small Cell Lung Cancer — 87a — Kimy Hernandez-Delacruz, Jillian Stamp, Ashley Nettifee, Calla Freesemann

Treatment of small cell lung cancer (SCLC), a lethal subtype of lung cancer, has seen little  progress in the last 40 years. The capacity of SCLC to acquire chemoresistance inflates its  likelihood of recurring to almost certainty, making sustained treatment success rates  dismal. These challenges necessitate further research into preventing SCLC from evading  available treatments or finding additional options to treat the disease. Key features that  differentiate SCLC from other lung cancers include the absence of functional p53 and RB1  tumor suppressors, as well as the presence of neuro-specific receptors due to the  neuroendocrine origin of the tumor. This study investigated the impact of two FDA approved migraine medications, Fosaprepitant and Rimegepant (Nurtec®), on SCLC.  Fosaprepitant served as a vehicle control, while Rimegepant targets the Calcitonin Gene  Related Peptide (CGRP) receptor expressed in SCLC. To evaluate the effects of these  medications, we performed Alamar Blue assays, colony forming assays, qPCR, and  immunofluorescence staining (IF). Alamar Blue Assays were used to assess patient derived SCLC human cell lines ability to proliferate in the presence of drug across  concentrations of 0, 15, 30, 80, and 100 µM. To study if the medications had any impact on  SCLC’s potential to metastasize, SCLC cell lines were treated with the drugs individually,  and their ability to grow from a single cell into a colony was examined using a colony  forming assay. IF staining and qPCR provided insight into CGRP receptor expression and  molecular subtype switching as a result of drug treatment. While proliferation rates appear  unchanged, there is potential for downstream gene expression changes. Further  investigation of neural signaling inhibition on SCLC could yield benefits for patients in the  future through drug repurposing.

Sanford Research
Michael Kareta