EL-20 - Recent advances in telomere biology for new cancer medicine

Abstract

While telomere shortening limits cell proliferation, telomerase maintains telomeres and causes immortality of cancer cells. Recent whole genome/exome sequencing of cancer has revealed recurrent mutations in telomere regulators, such as TERT and POT1, which reinforces an involvement of telomere abnormalities in cancer. Imetelstat, a telomerase inhibitor, has been tested in the clinical settings for many years. Recently, the compound has been found to cause clinical responses in myeloproliferative disorders, although the mode-of-action may not necessarily explain the efficacy. Meanwhile, the guanine-rich telomeric repeats can form a higher-order structure called G-quadruplex (G4). We have reported that G4-stabilizing compounds preferentially target glioma stem cells in preclinical models. From a potential diagnostic aspect, telomere length has been measured as a surrogate marker for disease and lifestyle. Intriguingly, cancer cells often keep their telomeres short, which allows upregulation of cancer-associated innate immune genes in a tumor microenvironment. In this lecture, I will overview these trends in telomere cancer biology and discuss perspective for new drug development.