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Chimeric fusion proteins--diphtheria toxin-based
A E Frankel1, B L Powell, D A Vallera
1Department of Medicine, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA. afrankel@wfubmc.edu
Abstract:
Most cancer patients receive chemotherapy drugs that target DNA or the cell division apparatus. Many of these patients develop multidrug-resistant tumor cells, thus, novel methods to overcome drug resistance are needed. One approach is to target tumor cell protein synthesis. Peptide toxins, which catalytically inactivate protein synthesis, have been re-engineered to selectively bind and intoxicate tumor cells. Diphtheria toxin (DT), a member of the class of peptide toxins, has been subjected to structural and genetic analysis and protein engineering for several decades. In this review, we will examine the structure, function, synthesis and pharmacology of anticancer DT conjugates.
Insights
Novel anticancer therapies targeting protein synthesis are needed to overcome drug resistance. This review examines engineered diphtheria toxin (DT) conjugates for selective tumor cell targeting and intoxication.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Chemotherapy resistance is a major challenge in cancer treatment, necessitating novel therapeutic strategies.
- Targeting tumor cell protein synthesis offers an alternative approach to overcome multidrug resistance.
- Diphtheria toxin (DT) is a peptide toxin that inhibits protein synthesis and has been extensively studied for protein engineering.
Purpose of the Study:
- To review the structure, function, synthesis, and pharmacology of anticancer diphtheria toxin (DT) conjugates.
- To explore the potential of engineered DT as a targeted cancer therapy.
- To discuss methods for overcoming drug resistance by targeting protein synthesis.
Main Methods:
- Review of existing literature on diphtheria toxin structure, function, and engineering.
- Analysis of studies on the development and application of DT conjugates in cancer research.
- Examination of pharmacological data related to DT-based anticancer agents.
Main Results:
- Diphtheria toxin (DT) can be engineered to selectively target and intoxicate cancer cells.
- Anticancer DT conjugates demonstrate potential in overcoming multidrug resistance.
- Structural and genetic modifications have enhanced the specificity and efficacy of DT-based therapies.
Conclusions:
- Engineered diphtheria toxin (DT) conjugates represent a promising strategy for targeted cancer therapy.
- Targeting protein synthesis with DT offers a viable alternative to conventional chemotherapy.
- Further research into the pharmacology and clinical application of DT conjugates is warranted.