We identified a gene environment interaction between DRD1 and secondhand smoke in relation to lung cancer risk--an observation that was seen in ever and never smokers. While dopamine signaling and its receptors are well characterized in the brain, there is a paucity of data regarding the role and the expression pattern of dopamine and its receptors in the normal lung. Previous studies have shown that dopamine plays an important role in bronchi-dilation and respiration, however a comprehensive analysis of dopamine, its receptors, transporters and metabolism has not been conducted. We are therefore mapping the dopamine axis in both normal lung tissue and human lung cancer. Our initial studies suggest that certain subtypes of the dopamine receptor family may function as tumor suppressors and we are currently validating those observations and investigating the molecular mechanism. In addition, we are examining the efficacy of specific dopamine receptor agonists and antagonists as therapeutic agents against cancer and analyzing the key mechanistic pathways involved.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIABC011555-06
Application #
10014727
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
6
Fiscal Year
2019
Total Cost
Indirect Cost
Name
National Cancer Institute Division of Basic Sciences
Department
Type
DUNS #
City
State
Country
Zip Code
Toulabi, Leila; Ryan, BrĂ­d M (2018) Stressing the need to overcome EGFR tyrosine kinase inhibitor resistance. Transl Lung Cancer Res 7:S123-S126
Robles, Ana I; Yang, Ping; Jen, Jin et al. (2014) A DRD1 polymorphism predisposes to lung cancer among those exposed to secondhand smoke during childhood. Cancer Prev Res (Phila) 7:1210-8