A5017932752- Cancer, Stress, Anesthesia, and Immune Response
- Neuropeptides and Animal Physiology
- Pharmacological Receptor Mechanisms and Effects
- Cancer, Hypoxia, and Metabolism
- Lung Cancer Research Studies
Columbia University
2019-2024
Columbia University Irving Medical Center
2024
Cancer Genetics (United States)
2019
<div>Abstract<p>The vagal nerve is linked to tumorigenesis in multiple tissues, including small cell lung cancer (SCLC). However, the role of sympathetic neurons SCLC development remains unknown. In this study, we observed a significant reduction tumor growth following chemical denervation local nerves mouse model SCLC. Further study identified that β2-adrenergic receptor (ADRB2) expression on cells mediated cross-talk with fibers. Genetic deletion or pharmacological inhibition...
<p>PKA inhibition (PKAi) reduces the growth of primary human SCLC cells</p>
<p>Co-culture with stellate ganglia (SG) promotes the growth of mouse SCLC</p>
<p>ADRB2 regulates the growth of human SCLC cells</p>
<p>High levels of ADRB2 promote the growth mouse SCLC</p>
<p>Sympathetic and parasympathetic nerve fibers in mouse SCLC</p>
<p>ICI treatment reduces the growth of SCLC</p>
SCLC is highly aggressive, with limited effective treatment options. We show that ablating sympathetic nerves or inhibiting the ADRB2 receptor slows progression and prolongs survival in mice. Additionally, inhibition reduces growth of human organoids xenografts by disrupting PKA signaling, identifying a new therapeutic target.
Abstract Glioblastoma harboring Fibroblast Growth Factor Receptor 3 (FGFR3)-Transforming Acidic Coiled-Coil containing (TACC-3) (FGFR3-TACC3) fusion is a distinct molecular subclass of tumors that can be targeted by FGFR kinase inhibitors. We generated knock-in mouse in which the expression FGFR3-TACC3 doxycycline inducible and reversible. The tetO-FGFR3-TACC3-IRES-GFP cassette was placed into Rosa26 locus strain intercrossed with GFAP-rtTA*M2 mice to trigger tetracycline transactivator (and...