Provided herein are, inter alia, methods of treating cancer by administering to a subject a therapeutically effective amount of an adenosine-A2A(A2A) receptor antagonist or a combination of an adenosine-A2A(A2A) receptor antagonist and a programmed cell death protein 1(PD-1) signaling pathway inhibitor. Further provided are pharmaceutical compositions including an A2Areceptor antagonist, a PD-1 signaling pathway inhibitor and a pharmaceutically acceptable excipient. Further provided are methods of detecting cellular effects, for example expression of pCREB, before, after or during adenosine receptor antagonist treatment.