In a recent study appearing in the journal Cancer Discovery, a research team have targeted telomeres with a small molecule called 6-thiodG that recruits the cell’s “biological clock” to kill cancer cells and shrink tumor block.

To prevent the cancer growth, the 6-thiodG molecule acts by targeting a unique mechanism that is thought to regulate how long cells can stay alive, a type of aging clock. This biological clock is defined by DNA structures known as telomeres, which become shorter every time the cell divides. Once telomeres have shortened to a critical length, the cell would enter into the apoptosis.

A new drug showed promising results

Investigators found that 6-thio-2′-deoxyguanosine could stop the growth of cancer cells in culture and decrease the growth of tumors in mice, and broad efficacy against a range of cancer cell lines with very low concentrations of 6-thiodG, as well as tumor burden shrinkage, appeared in the tested mice.

The successfully developed drugs can block telomerase, an RNA protein complex which makes telomeres in the adequate length, to trigger cell death and shrink tumor. The outcome occurrence after administering for long periods is partially because cells in any one tumor have chromosomes with different telomere lengths and any one cell’s telomeres must be critically shortened to induce death.

6-thiodG is preferentially used as a substrate by telomerase and disrupts the normal way cells maintain telomere length. Because 6-thiodG is not normally used in telomeres, the presence of the compound acts as an ‘alarm’ signal that is recognized by the cell as damage. As a result, the cell stops dividing and dies.

As known in the biomedical circle, telomerase is an almost universal oncology target, yet there are few telomerase-directed therapies in human clinical trials. To be remarkably encouraging, 6-thiodG potentially lead to positive effectiveness with minimal side effects in the blood, liver and kidneys of the mice that were treated with the molecule.

Reference:

Induction of Telomere Dysfunction Mediated by the Telomerase Substrate Precursor 6-Thio-2′-Deoxyguanosine. Cancer Discovery, 2014.