Xiaojie Liu, Rui Zhou, Ziliang Chu, Jie Liu
Far from being a mere epiphenomenon, acidosis is a pivotal factor in the somatic evolution of cancer and its progression toward malignancy. This review provides an inclusive overview of the mechanisms by which acidosis induces and selects for malignant phenotypes. We analyze enhanced invasion and metastasis, chemoresistance, immune surveillance suppression, and metabolic reprogramming. We also briefly examine the clinical development of small-molecule and antibody-based therapies targeting pH regulation. Furthermore, this review outlines various drug delivery and therapeutic systems that respond to extracellular and/or intracellular tumor pH, highlighting the advantages of nanomaterials in precision cancer therapy. With advances in artificial intelligence, nanotechnology is poised to expedite the screening of pH-responsive systems for preclinical research, promoting the development of personalized therapies and the mitigation of adverse reactions.