Cancer progression mechanism unravels clues to fight cancer

Researchers in Singapore have identified an important cancer progression mechanism that is observed in 90 per cent of cancer cells and this finding, they claim, will enable development that will halt cancer in its tracks and ultimately beat it with least side effects.

When it comes to normal cells, there is a definite lifespan and it is governed by telomeres, protective caps at the ends of chromosomes. As the cell multiplies over its life, these telomeres become shorter until eventually, they are too short to protect the DNA and the cell dies naturally. However, when it comes to cancer cells, these telomerase are reactivated and hence these cells never become inactive and continue to multiply.

By activating the Human Telomerase Reverse Transcriptase (hTERT) gene, cancer cells can continue to divide and multiply indefinitely in the body. Studies have shown that telomerase is reactivated in as much as 90 per cent of cancers, making hTERT, through which telomerase is activated, an excellent candidate for targeting cancer cells.

Current efforts to treat cancer by inhibiting telomerase with drugs have proven to be too toxic to patients due to the strong side effects on healthy cells. The research team has identified a specific DNA structure that forms only in cancer cells and brings the necessary molecular machinery into the correct position to activate the hTERT gene. The detailed mechanism of hTERT activation provided in this study would be instrumental in designing drugs to inhibit hTERT specifically in cancer cells with less side effects.

“Activation of telomerase is the most common oncogenic event providing immortality to cancer cells. We now know how to inhibit telomerase activity to target cancer cells specifically. This study will be a guide for developing next-generation cancer inhibitors,” said Semih Akincilar, Senior Research Fellow at A*STAR’s IMCB and lead researcher of the study.

Patient-derived colorectal cancer cell lines generated by GIS were utilised to identify correlative gene expression for hTERT activation and ascertain the physiological relevance of the findings in this study. These models will serve as a testbed for future studies aimed at the development of cancer-specific inhibitors of telomerase.

Building on this work, the team will collaborate with industrial and clinical partners to develop cancer-specific telomerase inhibitors and bring those candidates to the clinical stage.

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