Abstract
:A very promising direction in the development of anticancer drugs is inhibiting the molecular pathways that keep cancer cells alive and able to metastasize. Copper and iron are two essential metals that play significant roles in the rapid proliferation of cancer cells and several chelators have been studied to suppress the bioavailability of these metals in the cells. This review discusses the major contributions that Cu and Fe play in the progression and spreading of cancer and evaluates select Cu and Fe chelators that demonstrate great promise as anticancer drugs. Efforts to improve the cellular delivery, efficacy, and tumor responsiveness of these chelators are also presented including a transmetallation strategy for dual targeting of Cu and Fe. To elucidate the effectiveness and specificity of Cu and Fe chelators for treating cancer, analytical tools are described for measuring Cu and Fe levels and for tracking the metals in cells, tissue, and the body.
Highlights
In the U.S cancer is second only to heart disease for the leading causes of death and is soon expected to become the number one cause [1]
It has been shown that mixtures been shown that mixtures of PS and TSC increases the production of singlet oxygen, provoking of PS and TSC increases the production of singlet oxygen, provoking different types of cellular different types of cellular damage, including lipid peroxidation and accumulation of reactive oxygen species (ROS) in damage, including lipid peroxidation and accumulation of ROS in the mitochondria, due to the labile the mitochondria, due to the labile mitochondrial iron metabolism [191]
The use of Cu and Fe chelators, while likely not sufficient to combat cancer alone given the status of these metals as essential to the body, holds tremendous promise to be combined with other anticancer approaches
Summary
In the U.S cancer is second only to heart disease for the leading causes of death and is soon expected to become the number one cause [1]. The gold standard in the treatment of cancer remains the traditional approaches, surgery, radiation, and older drugs like cisplatin (and its second generation of compounds) but their success rates are extremely low and their applicability is limited [2]. Newer drugs, both broad and narrow spectrum, suffer from off target side effects and toxicity due to their lack of specificity for cancer cells and acquired cellular resistance. A very promising direction in the development of anticancer drugs is inhibiting the molecular pathways that keep cancer cells alive and able to metastasize. We briefly examine analytical tools that can be used to gauge the effectiveness of Cu and Fe chelators in inhibiting cancer growth and in targeting the cancer itself
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