Telomerase inhibition in hematologic malignancies 

Telomerase inhibition is grounded in discoveries by early Geron collaborators Elizabeth Blackburn, Carol Greider and Jack Szostak. Their work, which expanded the understanding of the role of telomeres and telomerase in highly proliferative diseases such as cancer, was awarded the 2009 Nobel Prize for Physiology or Medicine.

In the human body, normal growth and maintenance of tissues occurs by cell division. However, most cells are only able to divide a limited number of times, and this number of divisions is regulated by the length of telomeres, which are repetitions of a DNA sequence located at the end of chromosomes. Normally, every time a cell divides, the telomeres shorten. Eventually, they shrink to a critically short length, preventing further cell division or leading to cell death (apoptosis).

Telomerase is a naturally occurring enzyme that maintains telomeres and prevents them from shortening during cell division. Telomerase is upregulated in many malignant stem and progenitor cells, enabling their continued and uncontrolled proliferation, and driving tumor growth and progression. Telomerase expression has been found to be present in approximately 90% of biopsies taken from a broad range of human cancers.  Increased telomerase activity and human telomerase reverse transcriptase (hTERT) RNA expression have been reported in hematologic malignancies, including myelodysplastic syndromes (MDS). Thus, we believe that telomerase is a key molecular target in oncology.