Figure 2
(A) Conventional vs combinatorial therapy. With standard chemotherapy, tumour burden can initially result in a partial tumour reduction response, but almost universally a subset of resistant cells results in recurrence of disease. Thus, standard chemotherapy that does not affect telomere length will results in recurrence of disease with a similar average telomere length (eg, 7 kb). In contrast, combining chemotherapy with telomerase inhibitors should results in both a partial response and a gradual shortening of telomeres (right side of figure). There is every indication on the basis of preclinical research that small oligonucleotide readily enter all cancer cells. The hope is that both sensitive and chemotherapy-resistant cells may shorten their telomeres, eventually leading to more durable responses. (B) Telomerase inhibitors affect stem cells and cancer cell differently. It has been reported (unpublished results) using markers of cancer stem cells that telomeres are shorter compared with normal stem cells. Thus, there should be a window of opportunity to target cancer stem cells with short telomeres using telomerase inhibitors, leading to cancer stem cell depletion before normal stem cells become critically shortened.
