Scientists isolate telomerase as cancer drug target
stopping a gene from producing a protein that is essential for
cancer cell proliferation. The gene could form the basis for an
anti-cancer agent that targets this mechanism.
The gene produces telomerase, an enzyme that plays a central role in controlling the life span of cells by modifying structures called telomeres that are found at the end of chromosomes.
What's more, telomerase is not associated with benign tumours, representing a marker for malignant tumours only.
The team have been investigating breast cancer cells to identify the molecular signalling that is required to turn on, and also inhibit, the gene that produces telomerase.
The discovery that two proteins, Smad3 and c-Myc, were involved in turning off telomerase production is especially significant as finding inhibitors of telomerase and subsequently the pathway that inhibits telomerase in human cells could lead to drugs that target this pathway.
"It's the best indicator of cancer - 85 per cent better than any other tumour marker," said associate professor Jun-Ping Liu, from the Department of Immunology, Monash University.
"If we can control the production of telomerase we can prevent the immortality of cancer cells and therefore cancer formation," he added.
For most cancers to attain life-threatening characteristics, such as growing rapidly or metastasising throughout the body, the cancer cells must keep their telomeres from progressively shortening.
The activation of the enzyme telomerase is the means by which cancer cells accomplish this.
It maintains or increases telomere length and thereby increases the replicative lifespan of cells. Telomerase is not present or active in most normal cells and tissues, but it is activated during tumour progression. The presence of telomerase enables cancer cells to maintain long enough telomeres to keep dividing and growing.
If the activity of telomerase in cancer cells can be inhibited effectively, the normal process of telomere shortening and resulting cell senescence or death would dispose of most cancer cells before they became life-threatening.
"It's significant to find inhibitors of telomerase and we have found, for the first time, the pathway that inhibits telomerase in human cells," Liu said.
"This reveals an important mechanism for developing anti-cancer agents that mimic these proteins and thereby inhibit the production of telomerase."
The findings are published in the current issue of the Journal of Biological Chemistry.
