Thefirst A2AR orthosteric ligands, such as preladenant,imaradenant, taminadenant or ciforadenant (Figure 1), were developed for or derived from treatmentsfor Parkinson’s disease where adenosine concentrations arelower than in the TME.9 When repurposedas cancer immunotherapies, they resulted in low response rates and/orsafety concerns due to high dosing, leading to the discontinuationof most clinical trials. The gene discussed is ADORA2A; the disease is cancer.