Copper chelation in cancer therapy using tetrathiomolybdate: an evolving paradigm
1University of Michigan, Ann Arbor, MI, USA. gkhan@umich.edu
Expert Opinion on Investigational Drugs
|April 2, 2009
Summary
Tetrathiomolybdate (TM) shows promise as an anticancer and anti-angiogenic agent by chelating copper. Clinical trials in solid tumors indicate efficacy and a good safety profile, warranting further investigation.
Area of Science:
- Oncology
- Pharmacology
- Biochemistry
Background:
- Tetrathiomolybdate (TM) is an emerging agent with anticancer and anti-angiogenic properties.
- Its mechanism involves copper chelation and inhibition of NF-kappaB signaling pathways.
Purpose of the Study:
- To review the scientific basis for using Tetrathiomolybdate (TM) in human cancer studies.
- To consolidate evidence from preclinical, animal, and human trials.
Main Methods:
- A systematic literature review was performed.
- Studies included preclinical, animal, and human clinical trials of TM in cancer.
Main Results:
- TM demonstrated anti-angiogenic efficacy in preclinical and animal models through copper chelation.
- Phase I and II clinical trials in solid tumors showed TM to be effective with a favorable toxicity profile.
Conclusions:
- Copper chelation via TM is a viable anti-angiogenic strategy with demonstrated efficacy in various cancer models.
- TM exhibits therapeutic potential in solid tumors, supported by clinical trial data.
- The role of TM in cancer chemoprevention through copper lowering requires further research.
Related Concept Videos
02:57Targeted Cancer Therapies
The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against specific...
There are several types of targeted therapies against specific...
01:29Therapeutic Drug Monitoring: Affecting Factors
Therapeutic Drug Monitoring (TDM) is the clinical practice of measuring specific drug levels in a patient's blood or body tissues to manage and optimize therapy. TDM is crucial for drugs with narrow therapeutic windows, like warfarin and phenytoin, where incorrect doses can lead to treatment failure or severe side effects. This monitoring ensures the dosage administered is within a safe and effective range. The factors affecting therapeutic drug monitoring include:Patient-Specific Factors:a.
01:19Complexation Equilibria: The Chelate Effect
In complexation reactions, metal atoms or cations interact with ligands to form donor-acceptor adducts called metal complexes. Ligands that bind through one donor site are monodentate, ligands with two donor sites are bidentate, and those with more than two donor sites are polydentate ligands. For example, ethylene diamine is a bidentate ligand that binds through two nitrogen donor atoms, forming a five-membered ring. EDTA is a polydentate ligand that binds through four oxygen and two nitrogen...
02:51Metal-Ligand Bonds
The hemoglobin in the blood, the chlorophyll in green plants, vitamin B-12, and the catalyst used in the manufacture of polyethylene all contain coordination compounds. Ions of the metals, especially the transition metals, are likely to form complexes.
In these complexes, transition metals form coordinate covalent bonds, a kind of Lewis acid-base interaction in which both of the electrons in the bond are contributed by a donor (Lewis base) to an electron acceptor (Lewis acid). The Lewis acid in...
In these complexes, transition metals form coordinate covalent bonds, a kind of Lewis acid-base interaction in which both of the electrons in the bond are contributed by a donor (Lewis base) to an electron acceptor (Lewis acid). The Lewis acid in...
02:49Cancer Therapies
Cancer therapies are various modes of treatment, such as surgery, radiation therapy, and chemotherapy that are administered to cancer patients.
However, cancer treatments can pose several challenges, as therapies used to kill cancer cells are generally also toxic to normal cells. Moreover, cancer cells mutate rapidly and can develop resistance to chemical agents or radiation therapy. Besides, all types of cancer cells may not respond to the same therapy. Some cancer cells respond to one...
However, cancer treatments can pose several challenges, as therapies used to kill cancer cells are generally also toxic to normal cells. Moreover, cancer cells mutate rapidly and can develop resistance to chemical agents or radiation therapy. Besides, all types of cancer cells may not respond to the same therapy. Some cancer cells respond to one...
01:22EDTA: Chemistry and Properties
Polydentate ligands are most widely used in complexometric titrations because they form more stable complexes with the metal ions than mono- or bidentate ligands due to the chelate effect. Examples of polydentate ligands are ethylenediaminetetraacetic acid (EDTA), crown ethers, and cryptands. The most important feature of optimal polydentate ligands is the ability to form 1:1 complexes in a single-step process. Amino carboxylic acid derivatives are frequently used as complexing agents. EDTA is...