Prostate cancer is the leading cause of
cancer-related deaths in men.
Androgen ablation is the mainstay of treatment for advanced
prostate cancer. This
therapy is very effective in
androgen-dependent
cancer; however, these
cancers eventually become
androgen independent, rendering anti-
androgen therapy ineffective. The exploration of novel modalities of treatment is therefore essential to improve the prognosis of this
neoplasia. Telomeres are specialized
heterochromatin structures that act as protective caps at the ends of chromosomes. Telomere maintenance in the majority of
tumor cells is achieved by
telomerase, a
reverse transcriptase enzyme that catalyzes the synthesis of further telomeric
DNA.
Telomerase is detected in the majority of
prostate cancers, but not in normal or
benign prostatic hyperplasia tissue. Moreover, the human
telomerase reverse transcriptase (hTERT) gene, the catalytic subunit of
telomerase, is regulated by
androgens as well as by different oncogenes including Her-2, Ras, c-Myc and Bcl-2, which seem to play an important role in
prostate cancer progression. Thus,
telomerase may represent a very good candidate for targeted
therapy in prostate
tumors. To inhibit telomere maintenance by
telomerase, approaches that directly target either
telomerase and telomeres or the
telomerase regulatory mechanisms have been used. Moreover, strategies targeting
telomerase-positive cells as a means to directly kill the
tumor cells have been tested. This review summarizes the most promising results achieved by anti-
telomerase strategy in different solid
tumors. Most of the
telomerase-associated
therapies described here have proved very promising for the treatment of
prostate cancer. On the basis of the good results obtained and considering the multigenic defects of human
tumors, including
prostate cancer, the combination of anti-
telomerase strategies with conventional drugs and/or molecules capable of interfering with oncogenic pathways could efficiently improve the response of this
neoplasia.