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A Key to Cancer Research: The Origin-of-Life Molecule

The researchers discovered that inhibiting RNA synthesis with the THZ1 compound and analogs following therapies that cause DNA breakages, such as radiation therapy, dramatically improves tumor cells’ sensitivity to death.

Researchers from Spain and Denmark have discovered a technique for attacking cancer cells in the production of one of the origin-of-life molecules.

The molecule that gave rise to life, RNARibonucleic acid (RNA) is a polymeric molecule similar to DNA that is essential in various biological roles in coding, decoding, regulation and expression of genes. Both are nucleic acids, but unlike DNA, RNA is single-stranded. An RNA strand has a backbone made of alternating sugar (ribose) and phosphate groups. Attached to each sugar is one of four bases—adenine (A), uracil (U), cytosine (C), or guanine (G). Different types of RNA exist in the cell: messenger RNA (mRNA), ribosomal RNA (rRNA), and transfer RNA (tRNA).” data-gt-translate-attributes=”[{“attribute”:”data-cmtooltip”, “format”:”html”}]”>RNA, has been demonstrated to be important for repairing human genetic material and avoiding mutations that might lead to cancer development. Recent research breakthroughs, such as those reported by Daniel Gómez Cabello’s research team at the University of Seville, propose this compound as a therapeutic target for developing tailored cancer treatment strategies.

The RNA polymerase enzyme, the RNA production machine in cells, is required for safely and reliably repairing breaks in human DNADNA, or deoxyribonucleic acid, is a molecule composed of two long strands of nucleotides that coil around each other to form a double helix. It is the hereditary material in humans and almost all other organisms that carries genetic instructions for development, functioning, growth, and reproduction. Nearly every cell in a person’s body has the same DNA. Most DNA is located in the cell nucleus (where it is called nuclear DNA), but a small amount of DNA can also be found in the mitochondria (where it is called mitochondrial DNA or mtDNA).” data-gt-translate-attributes=”[{“attribute”:”data-cmtooltip”, “format”:”html”}]”>DNA. RNA production is essential for healthy cells, but it is extremely important for tumor cells, which need considerably higher activity from this enzyme to grow uncontrollably.

The research showed that following DNA-damaging treatments, such as radiation therapy, RNA synthesis inhibition with the THZ1 compound and analogs significantly increases tumor cells’ sensitivity to death.

“This study provides clues on how to improve conventional therapies and achieve a higher success rate with treatments. Although there is still a long way to go to be able to use these RNA polymerase inhibitors in the clinical setting, clinical trials are currently underway based on this enzyme for treating cancer”, explained the Principal Investigator, Daniel Gómez-Cabello.

“Increasing the knowledge on how to use these compounds in a safer and more tailored manner allows us to address as best as possible the treatment of cancer,” added the researcher Diana Aguilar-Morante, the study’s co-author.

This research by the Biomedical Institute of Seville and the University of Seville, in collaboration with the Danish Cancer Society, has been published in the prestigious journal Nature CommunicationsNature Communications is a peer-reviewed, open access, multidisciplinary, scientific journal published by Nature Research. It covers the natural sciences, including physics, biology, chemistry, medicine, and earth sciences. It began publishing in 2010 and has editorial offices in London, Berlin, New York City, and Shanghai. ” data-gt-translate-attributes=”[{“attribute”:”data-cmtooltip”, “format”:”html”}]”>Nature Communications. Both researchers return to Spain from Denmark and have been able to continue their research thanks to contracts funded by the Government of Andalusia and the Spanish Association against Cancer (AECC).

“Thanks to the AECC, we have been able to continue with these studies and move this project forward,” explained the author.

Currently, these researchers are working on the mechanisms of how RNA, the original molecule that enables life, can serve as a tool for treating diseases.


“Once we have observed that selectively inhibiting RNA production boosts the utility of radiation therapy in cancer cells and does not drastically affect the rest of the cells, we will start researching it in various types of cancer, such as glioblastoma and pediatric neuroblastoma,” commented Diana Aguilar-Morante. “At this point, our challenge will be to improve the efficiency of these new RNA production inhibitors and reduce the side effects that can occur in patients with cancer,” stated Gómez-Cabello.

Reference: “CtIP-dependent nascent RNA expression flanking DNA breaks guides the choice of DNA repair pathway” by Daniel Gómez-Cabello, George Pappas, Diana Aguilar-Morante, Christoffel Dinant and Jiri Bartek, 9 September 2022, Nature Communiations.
DOI: 10.1038/s41467-022-33027-z


Source: SciTechDaily