Related Experiment Video
Updated: Jul 8, 2026
11:14
Anticancer Metal Complexes: Synthesis and Cytotoxicity Evaluation by the MTT Assay
Published on: November 10, 2013
Matrix metalloproteinase inhibitors as anticancer agents.
Panagiotis A Konstantinopoulos1, Michalis V Karamouzis, Athanasios G Papatsoris
1Department of Biological Chemistry, Medical School, University of Athens, 11527 Athens, Greece.
The International Journal of Biochemistry & Cell Biology
|January 1, 2008
Summary
Matrix metalloproteinase inhibitors (MMPIs) show promise in preclinical cancer models but have largely failed in clinical trials. This review explores MMP roles in cancer and discusses strategies to improve MMPI efficacy.
Area of Science:
- Oncology
- Biochemistry
- Pharmacology
Background:
- Matrix metalloproteinases (MMPs) play a significant role in cancer development (carcinogenesis).
- MMP inhibitors (MMPIs) demonstrated potent anticancer activity in preclinical studies.
- Clinical trials of MMPIs in advanced human malignancies have yielded disappointing results, lacking significant survival benefits.
Purpose of the Study:
- To review the role of MMPs in carcinogenesis.
- To outline the pharmacology and clinical status of MMPIs as anticancer agents.
- To discuss reasons for the discrepancy between preclinical and clinical findings for MMPIs.
- To propose strategies for integrating MMPIs into current cancer therapies.
Main Methods:
- Literature review of MMPs in carcinogenesis.
- Analysis of MMPI pharmacology and clinical trial data.
- Discussion of preclinical-clinical discrepancies.
- Formulation of strategic recommendations for MMPIs in oncology.
Main Results:
- MMPs are crucial in various stages of cancer progression.
- Despite preclinical success, MMPIs have not translated into significant clinical survival benefits for most cancers.
- Several factors contribute to the failure of MMPIs in clinical settings, including pharmacokinetic/pharmacodynamic issues and tumor heterogeneity.
Conclusions:
- The established role of MMPs in cancer necessitates further investigation into effective therapeutic strategies.
- Understanding the reasons for clinical trial failures is critical for future MMPI development.
- Novel approaches and combination therapies are needed to harness the potential of MMPIs in cancer treatment.
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...
01:10Drugs that Destabilize Microtubules
Microtubules are dynamic structures and can be regulated by microtubule targeting agents (MTAs). Microtubule destabilizing drugs are a class of MTAs that destabilize and prevent microtubules' polymerization. Both natural and synthetic chemicals can be found under this class of drugs. Vincristine and vinblastine, two vinca alkaloids, and colchicine were among the first to be discovered. These drugs can affect cells in various ways, either by inducing a change in cell morphology, preventing...
01:23Role of Matrix Metalloproteases in Degradation of ECM
Matrix metalloproteases (MMPs) are enzymes involved in the hydrolysis of proteins and glycoproteins of the extracellular matrix. MMPs are essential for the migration and proliferation of cells through the dense matrix network, throughout embryonic development, and throughout morphogenesis. The first MMP activity discovered was a collagenase in a tadpole's tail undergoing metamorphosis. The active collagen deposition and modifications lead to the morphogenesis of tadpoles into the adult body.
A...
A...
01:15Drugs that Stabilize Microtubules
Microtubules are dynamic structures that undergo cycles of catastrophe and rescue. The microtubules play a central role in cell division by forming the spindle apparatus for segregating the chromosomes. This makes them ideal targets for regulating dividing cells in tumors and malignant cancer cells. Microtubule stabilizing drugs help stabilize the microtubule formation and promote its polymerization. Paclitaxel was the first microtubule stabilizing agent used as anticancer drug in chemotherapy...
02:38Mitogens and the Cell Cycle
Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
02:30Metastasis
Metastasis is the spread of cancer cells from the original site to distant locations in the body. Cancer cells can spread via blood vessels (hematogenous) as well as lymph vessels in the body.
Epithelial-to-Mesenchymal Transition
The epithelial-to-mesenchymal transition or EMT is a developmental process commonly observed in wound healing, embryogenesis, and cancer metastasis. EMT is induced by transforming growth factor-beta (TGF-β) or receptor tyrosine kinase (RTK) ligands, which further...
Epithelial-to-Mesenchymal Transition
The epithelial-to-mesenchymal transition or EMT is a developmental process commonly observed in wound healing, embryogenesis, and cancer metastasis. EMT is induced by transforming growth factor-beta (TGF-β) or receptor tyrosine kinase (RTK) ligands, which further...