Targeted inhibition of telomerase in human cancer: will it be a double-edged sword?

S Sasgary1, M Wieser, C Cerni

  • 1Institut für Tumorbiologie-Krebsforschung, Universität Wien.

Onkologie
|July 7, 2001
PubMed

Insights

Telomerase, an enzyme crucial for cancer cell growth, offers potential as an anti-cancer target. Inhibiting telomerase may halt tumor progression, but further research is needed to address potential side effects.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cell Biology

Background:

  • Most human cancers (over 80%) exhibit telomerase activity, unlike normal somatic cells.
  • Normal cell division leads to telomere shortening due to the 'end-replication problem', causing cell cycle arrest and death.
  • Telomeres are protective DNA sequences at chromosome ends; their critical shortening limits cellular lifespan.

Purpose of the Study:

  • To investigate the role of telomerase in cancer cell proliferation and immortalization.
  • To evaluate the potential of telomerase inhibition as an anti-cancer therapeutic strategy.
  • To explore the implications of telomerase activation and inhibition in cellular growth and cancer development.

Main Methods:

  • Studied telomerase activity in human malignancies versus normal tissues.
  • Utilized transfection of telomerase reverse transcriptase (TERT) constructs in normal human cell types.
  • Examined the effects of telomerase inhibition in cancer cell lines.

Main Results:

  • Telomerase, a ribonucleoprotein complex (RNA (TR) and catalytic subunit (TERT)), adds telomeric repeats to chromosome ends.
  • TERT transfection led to telomere elongation, stabilization, and immortalization of normal human cells.
  • Inhibition of telomerase in cancer cell lines resulted in growth arrest in initial experiments.

Conclusions:

  • Telomerase activation is a key factor in the continuous growth of tumor cells.
  • Targeting telomerase may offer a promising approach for adjuvant cancer therapy.
  • Concerns exist regarding the broad application of telomerase inhibition strategies in cancer treatment.

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