Metabolic Inhibitors and their Impact on Cancer Cell Migration, Invasion, and Metastasis.

Abstract

Cancer metastasis, the process by which cancer cells spread from the primary tumor to distant sites, remains the leading cause of cancer-related deaths. Th s complex process involves a series of steps, including cell detachment, migration, invasion, survival in the circulatory system, extravasation, and colonization of new tissues. A fundamental characteristic of cancer cells is their altered metabolism, often exhibiting increased glucose uptake and a preference for glycolysis even in the presence of oxygen, a phenomenon known as the Warburg effect. Th s metabolic shift provides cancer cells with a rapid source of adenosine triphosphate (AtP) and essential biosynthetic intermediates, supporting their rapid growth and proliferation. While early concepts attributed the Warburg effect to mitochon- drial dysfunction, it is now recognized that mitochondria in cancer cells often remain functionally active, including oxidative phosphorylation, and critically regulate tumor progression. Notably, metastatic cells frequently depend on mitochondrial activity, refl cting metabolic plasticity that supports dissemination. Thus, targeting glycolysis-mito- chondria crosstalk may represent a promising antimetastatic therapeutic strategy. Th s review aims to elucidate the mechanisms by which inhibitors of glycolysis and OXPhOS impact cancer cell migration, invasion, and metastasis, and to explore their potential therapeutic applications.