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. We will also evaluate the effect of dopamine on the immune system in these animal models of lung cancer as, in addition to functioning as an inhibitor of angiogenesis, recent work shows that CD4 and CD8 T cells express dopamine receptors. Moreover, these cells synthesize and transport dopamine. T cells from patients with PD have reduced dopamine receptor immunoreactivity, suggesting that the connection between dopamine and cancer could involve the immune system. We are also conducting an analysis of anti-depressant use among lung cancer patients to ask whether these patients have a better or worse outcome compared to those not taking anti-depressants. As many anti-depressants function as dopamine agnonists and antagonists, if dopamine is a bone fide tumor suppressor, this research could have implications for repositioning of this drug class towards cancer treatment.
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