Inducing cancer cell death has always been a research hotspot in life sciences. With the continuous deepening and diversification of related research, the potential value of metal elements in inducing cell death has been explored. Taking iron as an example, ferroptosis, mainly characterized by increasing iron load and driving the production of large amounts of lipid peroxides and eventually leading to cell death, has recently attracted great interest in the cancer research community. After iron, copper, a trace element, has received extensive attention in cell death, especially in inducing tumor cell death. Copper and its complexes can induce autophagy or apoptosis in tumor cells through a variety of different mechanisms of action (activation of stress pathways, arrest of cell cycle, inhibition of angiogenesis, cuproptosis, and paraptosis), which are promising in cancer therapy and have become new hotspots in cancer treatment research. This article reviews the main mechanisms and potential applications of novel copper and copper compound-induced cell death, focusing on copper compounds and their anticancer applications.

Oral drugs classified under Class III of the Biopharmaceutics Classification System (BCS) are defined by high aqueous solubility yet low intestinal permeability. Their restricted oral bioavailability arises not from inadequate dissolution, but is primarily governed by the intestinal permeability barrier, coupled with substantial inter-individual variability in absorption. This review adopts the intestinal permeability barrier as its core analytical framework to dissect the key determinants of oral absorption for BCS III drugs, while presenting a comparative and critical evaluation of prevailing bioavailability enhancement strategies. From perspectives including mechanism of action, achievable magnitude of enhancement, applicable physicochemical and physiological conditions, and translational feasibility, the intrinsic mechanistic limitations and applicable boundaries of distinct strategies are delineated. Finally, this paper concludes that the absorption barriers of BCS III drugs cannot be universally surmounted by a single strategy, emphasizing the significance of mechanism-guided strategy selection for the rational design of oral drug delivery systems. In doing so, it provides a foundational basis for the rational development of oral delivery systems tailored to BCS III drugs.