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Peptide toxins directed at the matrix dissolution systems of cancer cells
Arthur E Frankel1, Thomas H Bugge, Shihui Liu
1Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.
Abstract:
Growth and spread of tumors requires a variety of membrane and extracellular proteases to modify membrane integrins, dissolve the surrounding matrix and release critical growth factors from both the tumor cell surface and surrounding structures. The two major protease systems involved in this process are the matrix metalloproteases and the serine proteases. Genes and gene products for both protease systems are overexpressed in a variety of neoplasms. Thus, these enzymes serve as excellent targets for the delivery of potent cytotoxic molecules to tumors. A number of peptide toxins have been engineered to bind to tumor cells with high levels of surface proteases and their receptors including anthrax toxins, Pseudomonas exotoxin, saporin and diphtheria toxin. These recombinant fusion proteins provide a novel class of anti-cancer agents that will enter clinical trials in the next several years.
Insights
Cancer growth relies on proteases, which are overexpressed in tumors. Engineered toxins targeting these proteases offer a novel anti-cancer therapy entering clinical trials.
Area of Science:
- Biochemistry
- Molecular Biology
- Oncology
Background:
- Tumor growth and metastasis depend on membrane and extracellular proteases.
- Matrix metalloproteases and serine proteases are key enzyme systems involved.
- These protease systems are frequently overexpressed in various neoplasms.
Purpose of the Study:
- To explore the potential of targeting overexpressed proteases in cancer.
- To investigate the use of engineered toxins for targeted cancer therapy.
Main Methods:
- Engineering peptide toxins to bind to tumor cell surface proteases and receptors.
- Utilizing toxins such as anthrax toxin, Pseudomonas exotoxin, saporin, and diphtheria toxin.
Main Results:
- Engineered toxins demonstrate specific binding to tumor cells with high protease levels.
- These toxins represent a novel class of anti-cancer agents.
Conclusions:
- Overexpressed proteases in tumors are viable targets for therapeutic intervention.
- Recombinant fusion proteins offer a promising new avenue for cancer treatment.