HCAR1 and non-small cell lung carcinoma: For example, mild acidic stress not only facilitates unfolded protein response (UPR) but also triggers an adaptive UPR with progressive increase in glucose regulatory protein 78 expression, which reduces the cleavage of caspase 7 to induce sunitinib resistance in oral squamous cancer (212, 224); extracellular lactate functions as an agonist for G protein-coupled receptor 81 (GPR81) and promotes GPR81 upregulation of the PI3K/AKT/mTOR pathway to inhibit apoptosis, promote stem cell phenotype, inhibit immune response, and induce etoposide resistance in non-small-cell lung cancer (234, 236).