Toxic metal ions in the tumor microenvironment

Toxic metal ions in the tumor microenvironment (TME) refer to the dysregulated and often elevated concentrations of transition metals, such as copper, iron, and zinc, that facilitate tumor progression. These ions act as essential cofactors for a variety of enzymes that drive the hallmarks of cancer, including those involved in angiogenesis, metabolic reprogramming, and the epithelial-mesenchymal transition (Torti & Torti, 2013, Nature Reviews Cancer). For instance, copper is a critical requirement for the activity of lysyl oxidase (LOX) and vascular endothelial growth factor (VEGF), which are central to metastasis and blood vessel formation (Brewer, 2005, Current Opinion in Chemical Biology). Iron is frequently sequestered by malignant cells to support rapid DNA synthesis and mitochondrial bioenergetics (Ge et al., 2022, Signal Transduction and Targeted Therapy). Therapeutic strategies targeting these ions include chelation therapy to deplete the local metal supply or the development of metal-ion-responsive prodrugs and nanoparticles that release cytotoxic payloads specifically within the ion-rich TME (Gupte & Mumper, 2009, Cancer Treatment Reviews). However, because these metals are also vital for normal physiological processes, achieving selective intratumoral depletion without inducing systemic toxicity remains a primary challenge for drug development.

Other names

Intratumoral metal ionsHeavy metal ions in TMELabile metal poolTumor-associated metal ionsTransition metals in cancer

Sequestration of essential metal cofactors via chelation to inhibit tumor growth and angiogenesis, or utilization of high ion concentrations to trigger site-specific drug release from responsive nanocarriers.