Adenosine A2A Receptor: A Prognosis Marker For Lung Cancer
National Jewish Health
The role of angiogenesis in tumor survival and metastasis is now well recognized. Hypoxia-inducible transcription factors HIF-1alpha and HIF-2alpha are both known to induce angiogenesis by up regulating a common set of cytokines, including VEGF, but only the activation of HIF-2alpha has been associated with poor prognosis in lung cancer. However, since HIF-2alpha is highly labile, it is a poor candidate for a biomarker.
Scientists at National Jewish Health have discovered that the receptor Adenosine A2A (ADORA2A) is expressed only in response to HIF-2alpha activation and more importantly that the expression of ADORA2A is increased in later stage lung tumors.
This receptor could therefore be used as a prognosis marker for lung cancer as well as a potential new target for an anti-angiogenic approach to treating lung cancer.
- A biomarker for HIF-2alpha activation and therefore for poor prognosis in lung cancer.
- A target for anti-angiogenic therapy in lung cancer
Advantages of Invention
Since HIF-2alpha is too labile to be used as a marker, ADORA2A instead can be used as readout of HIF-2alpha activation and can be easily measured at the RNA level in biopsy samples.
State of Development
- Our scientists have found that Hypoxia increases ADORA2A in vitroHIF-2alpha and not HIF-1alpha regulates ADORA2A expression
- Over expression of ADORA2A or its activation through agonists leads to an increase in endothelial cell proliferation, migration, and branching ADORA2A expression increases in later stage tumor samples collected from lung cancer patients
Ahmad et.al. Proc Natl Acad Sci U S A. 2009 Jun 30;106(26):10684-9. Epub 2009 Jun 17.
U.S. patent application #20090155796. International patent publication #WO2009/065044.
Aftab Ahmad, PhD and Carl White, MD
Available for licensing.