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What role does telomerase play in cancer?
Telomerase is the enzyme that replenishes shortened telomeres and allows cells to reproduce indefinitely. Found in only a few normal human cells, telomerase is present in as many as 90% of human cancers. This makes telomerase an attractive candidate for highly selective cancer drugs.
The evidence that activation of telomerase is necessary for most cancers to thrive is strong. Indeed, some scientists believe that telomerase activation is the main pathway by which cancer cells become immortal, that is, able to reproduce forever without limits. Most normal human cells can only undergo 30-50 doublings before their telomeres are too short and doubling stops. Cancer cells must undergo about 80 doublings before a tumor mass is large enough to be detected. Thus, say researchers, telomerase activation is necessary for most cancers to grow.
A number of researchers have suggested that if telomerase is required for so many cancers to flourish, perhaps anti-telomerase drugs could be developed as cancer-fighting agents. Some have suggested that such a drug would have minimal side effects, since so few normal cells have active telomerase. Others caution that some side effects are possible. Some normal cells, including stem cells, normally have telomerase activity and might be affected adversely by anti-telomerase drug therapy. Those potential side effects include:
- Blood toxicity: Some populations of stem cells, which are the parents of mature blood cells, do use telomerase. Anti-telomerase drugs could, therefore, suppress the production of vital blood cells.
- Immune toxicity: Some infection-fighting cells use telomerase normally. Anti-telomerase drugs, therefore, could theoretically weaken our ability to fight infection.
- Skin toxicity: While most of our skin cells have little telomerase activity, those that repair wounds do have some. Anti-telomerase drugs might cause delayed wound healing.
- Gonadal toxicity: Some normal telomerase activity is seen in the cells of the ovary and testis. Thus, anti-telomerase drugs could potentially interfere with fertility, although this is still speculative.
One drawback to the use of anti-telomerase drugs in the treatment of cancer is the length of time needed for such drugs to have any effects. If telomerase is not activated until numerous generations of cell division have shortened telomeres to critical lengths, tumor cells could have doubled thirty or more times before telomerase is turned on. Even if anti-telomerase drugs were developed in the near future, they would need to be used in conjunction with faster-acting anti-cancer drugs.
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