Potential therapeutics using tumor-secreted lactate in nonsmall cell lung cancer

•Non-small cell lung cancer (NSCLC) frequently presents genetic mutuations.•NSCLC upregulates glucose metabolism and subsequent accumulates lactate.•Lactate as key molecule leads various phenomena in tumor microenvironment.•Lactate oxidase (LOX) can directly oxidize tumor-secreted lactate.•Consuming or oxidizing tumor-secreted lactate provides a potential route. Targeted-therapy failure in treating nonsmall cell lung cancer (NSCLC) frequently occurs because of the emergence of drug resistance and genetic mutations. The same mutations also result in aerobic glycolysis, which further antagonizes outcomes by localized increases in lactate, an immune suppressor. Recent evidence indicates that enzymatic lowering of lactate can promote an oncolytic immune microenvironment within the tumour. Here, we review factors relating to lactate expression in NSCLC and the utility of lactate oxidase (LOX) for governing therapeutic delivery, its role in lactate oxidation and turnover, and relationships between lactate depletion and immune cell populations. The lactate-rich characteristic of NSCLC provides an exploitable property to potentially improve NSCLC outcomes and design new therapeutic strategies to integrate with conventional therapies.