New discovery in cancer progression paves way to cancer drugs with fewer side effects

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Graphic design. Credit: Analysis of Nucleic Acids (2022). DOI: 10.1093/nar/gkac479

Scientists from A*STAR’s Institute of Molecular and Cell Biology (IMCB) and Genome Institute of Singapore (GIS), as well as NUS Cancer Science Institute of Singapore (CSI Singapore), National Cancer Center Singapore (NCCS) and Nanyang Technological University. NTU), have discovered an important mechanism of cancer development that is observed in 90% of cancer cells. This research will lead to further development of specific cancer drugs with potentially fewer side effects. The study, led by the IMCB, is published in the journal Analysis of Nucleic Acids on 14 June 2022.

A healthy cell’s lifespan is determined by telomeres, the protective caps at the ends of chromosomes. Every time a cell divides, the telomeres become shorter to the end, they are too short to protect the DNA and the cell literally dies. In contrast, cancer Cells survive by reactivating telomerase, an enzyme that can lengthen telomeres, but is inactive in most adult cells.

By activating Human Telomerase Reverse Transcriptase (hTERT), cancer cells can continue to multiply in the body indefinitely.

Studies have shown that telomerase is reactivated in about 90 percent of cancers, making hTERT, a pathway through which telomerase is activated, a good candidate for targeting cancer cells.

Current efforts to treat cancer by inhibiting telomerase with drugs have proven to be toxic to patients due to a strong effect on healthy cells. The research team identified a specific DNA sequence that is only found in cancer cells and brought the necessary genetic material into the correct position to activate the hTERT gene. The detailed hTERT activation model provided in this study will be a tool to design drugs to specifically inhibit hTERT in cancer cells with less side effects.

“Activation of telomerase is the most common oncogenic event that provides immortality to cancer The cells. We now know how to target telomerase activity cancer cells especially. This research will be a guide for the development of future cancer inhibitors,” said Semih Akincilar, Chief Research Officer at A*STAR’s IMCB and lead researcher of the study.

Cancer cell lines obtained from patients generated by GIS were used to detect gene expression for hTERT activation and to confirm the physiological relevance of the findings in this study. These samples will serve as a test case for future studies aimed at developing cancer-specific telomerase inhibitors.

Building on this work, the team will collaborate with industry and clinical partners to develop specific cancer treatments. telomerase inhibitors also bring these candidates to the clinical stage.

Researchers have discovered a new mechanism by which telomerase works to keep cancer cells from growing

More information:
Semih Can Akıncılar et al, Discovery of a cancer cell-specific reactivation pathway of hTERT provides therapeutic opportunities to block telomerase specifically in human cancers, Analysis of Nucleic Acids (2022). DOI: 10.1093/nar/gkac479

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