Evaluation of telomerase-targeted therapies in canine cancer cell lines.
Despite advances in conventional therapeutics, cancer remains an invariably fatal disease, the major challenge being to develop tumour-specific cancer treatment strategies. Current treatments such as chemotherapy and radiotherapy rely on a crude distinction between cancer cells and normal cells. However, with an increased understanding of the molecular events in the development of cancer, it is possible that far more innovative and targeted approaches can be developed. From studies on humans and dogs, the enzyme telomerase has emerged as a central unifying mechanism underlying the immortal phenotype of cancer and has thus become a candidate for differentiating between normal and cancer cells. The level and frequency of telomerase activity and component gene expression in cancers reinforces this as a potential target for cancer therapies. This article describes two approaches to target cancer by capitalizing on the expression of this enzyme. In the first approach, we target the enzyme itself, the goal being to cause cancer cell death. In the second approach, we utilize the respective gene promoters for telomerase component enzymes to drive expression of a reporter gene in cancer cell lines. The results demonstrated that targeted gene expression using promoter elements can be achieved specifically in telomerase-positive cell lines. However, targeting the enzyme itself proved less successful and warrants investigations into alternative approaches.
Argyle
D J
DJ
Department of Medical Sciences, School of Veterinary Medicine, University of Wisconsin Comparative Oncology Program, Madison, WI 53706-1102, USA. argyled@svm.vetmed.wisc.edu
McKevitt
T
T
Gault
E
E
Nasir
L
L