In colorectal cancer (CRC), lactate activates the GPR81/adenosine 3′,5′-monophosphate (cAMP)/protein kinase A (PKA)/CREB (cAMP response element-binding protein) signaling axis, which suppresses MLH1 expression, thereby impairing mismatch repair processes and promoting chemoresistance [44]. The gene discussed is HCAR1; the disease is colorectal carcinoma.