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A tumorigenic microenvironment can give rise to neoplasm. A shift from this condition to a tumor-suppressive microenvironment is of significant benefit to susceptible individuals. The carbonyl groups of glycine and valine have long bond lengths, consequently generating potent affinities to divalent cations such as calcium. We hypothesize that the formation of insoluble and rigid calcium oxalate augmented by glycine and valine counteracts strong acids such as HCl chemically, thus reducing cancer risks. The anticancer effects of the 2 amino acids can be explained from a chemical and biochemical perspective. A tumor-suppressive microenvironment could be established via the modification of the proteome without genome editing at the DNA level.

Numerous cases of checkpoint inhibitor–triggered cancer hyperprogression have been documented. A previous hypothesis attributes cancer onset to the local buildup of hydrogen chloride, jointly mediated by hydrogen bond donors and acceptors and basic amino acids. The anti-PD1/PD-L1 immunotherapies may have caused a surge of protons or chloride ions for the effective treatment of neoplasm, thus giving rise to the local formation of hydrogen chloride and subsequently cancer hyperprogression in some susceptible individuals. It was postulated that the local strength of acidity is critical for tumor growth and metastasis, as the intake of weak organic acids reduces cancer risks. The anti-PD1/PD-L1 immunotherapies can be integrated with weak organic acids to reduce adverse reactions and generate better anticancer outcomes.