Diphtheria Fusion Protein Therapy of Chemoresistant Malignancies

Authors: Frankel A.E.; Rossi P.; Kuzel T.M.; Foss F.

Source: Current Cancer Drug Targets, Volume 2, Number 1, March 2002 , pp. 19-36(18)

Publisher: Bentham Science Publishers

Abstract:

Patients with widespread cancer respond initially to combination chemotherapy, immunotherapy, and / or radiotherapy, but most relapse with chemoresistant disease. Novel methods of killing resistant neoplastic stem cells are needed. One such approach is therapy with targeted toxins composed of tumor cell selective ligands covalently linked to group I peptide toxins (group II and III peptide toxins act on the cell surface). The targeted toxin is delivered to the cell by a tumor selective ligand. Once bound, the ligandreceptor complex is internalized. The catalytic domain escapes to the cytosol. The toxin then enzymatically modifies a critical cell function (protein synthesis, p21 Rho activity, protein kinase signaling, cyclic AMP signaling or others). The irreversibly damaged cells fails to divide and, eventually, undergoes lysis or programmed cell death. Targeted peptide toxins used to date in the treatment of chemotherapy refractory cancers include ricin toxin, Pseudomonas exotoxin, pokeweed antiviral protein, saporin, gelonin and diphtheria toxin. In this review, we have focused on the applications of genetically engineered diphtheria toxin for cancer therapy.

Keywords: Diphtheria Fusion Protein Therapy; Chemoresistant Malignancies; Pseudomonas exotoxin; saporin; gelonin; diphtheria toxin; genetically engineered diphtheria toxin; cancer therapy; corynebacterium diphtheriae; iymphocytic leukemia cll

Language: English

Document Type: Review article

DOI: http://dx.doi.org/10.2174/1568009023333944

Publication date: 2002-03-01

• Current Cancer Drug Targets aims to cover all the latest and outstanding developments on the medicinal chemistry, pharmacology, molecular biology, genomics and biochemistry of contemporary molecular drug targets involved in cancer, e.g. disease specific proteins, receptors, enzymes, genes.
  Each issue of the journal contains a series of timely in-depth reviews written by leaders in the field covering a range of current topics on drug targets involved in cancer.
  As the discovery, identification, characterization and validation of novel human drug targets for anti-cancer drug discovery continues to grow; this journal has become essential reading for all pharmaceutical scientists involved in drug discovery and development.

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• In this Subject: Oncology ,  Pharmacology
• By this author: Frankel A.E. ;  Rossi P. ;  Kuzel T.M. ;  Foss F.

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