[Mar. 29, 2023: María García Gordillo, University of Seville]
RNA, the molecule that gave rise to life, has been shown to be essential for repairing human genetic material. (CREDIT: Creative Commons)
Scientists have long known that RNA, the molecule that gave rise to life, plays a crucial role in the functioning of living cells. Now, new research from the University of Seville suggests that RNA may hold the key to developing tailored strategies for treating cancer.
According to a recent study led by Daniel Gómez Cabello, an expert in DNA damage and repair, and his team at the Biomedical Institute of Seville and the University of Seville, RNA is essential for repairing human genetic material and preventing mutations that might lead to cancer. The RNA polymerase enzyme, which is responsible for producing RNA in cells, is especially crucial for healthy cells and is required in greater amounts by tumor cells to grow uncontrollably.
The study, which was published in the prestigious journal Nature Communications, revealed that inhibiting RNA synthesis with the THZ1 compound and analogues after therapies that cause DNA breakages, such as radiation therapy, greatly increases tumor cells' sensitivity to death. This finding could have significant implications for cancer treatment, as it suggests that targeting RNA production could be a promising therapeutic strategy.
“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.
The researchers hope that this discovery could lead to the development of more effective cancer treatments that specifically target tumor cells while sparing healthy ones. While there is still much research to be done before RNA-targeted therapies can be used in the clinic, the team is optimistic about the potential of their findings.
“Increasing the knowledge on how to use these compounds in a safer and more tailored manner allows us to address the treatment of cancer as best as possible”, added the researcher Diana Aguilar-Morante, the study’s co-author.
The Road to RNA-Based Cancer Therapies
The idea of using RNA-based therapies to treat cancer is not a new one. In fact, researchers have been exploring the potential of RNA-targeted therapies for several years now. However, until recently, the technology required to develop these therapies was not advanced enough to make them a reality.
DNA resection (ssDNA) correlates with nascent RNA synthesis. (CREDIT: Nature Communications)
Thanks to recent advances in genomics and biotechnology, however, scientists are now able to design RNA molecules that can target specific genes and pathways in tumor cells. This has opened up a new avenue for cancer research and could potentially lead to the development of highly targeted, personalized treatments that are more effective and less toxic than current therapies.
The research by Gómez Cabello and his team is an important step forward in this area. By showing that inhibiting RNA synthesis can make tumor cells more vulnerable to radiation therapy, the study provides a proof of concept for the idea of using RNA-targeted therapies in cancer treatment.
Nascent RNAs colocalize with DNA resection tracts in irradiated HeLa cells. (CREDIT: Nature Communications)
However, the road to RNA-based cancer therapies is still a long one. There are many challenges that need to be overcome before these therapies can become a reality. One of the biggest challenges is finding ways to deliver RNA molecules to tumor cells without causing harm to healthy cells.
Another challenge is improving the efficiency of RNA production inhibitors and reducing the side effects that can occur in patients with cancer. This will require further research and development, as well as extensive testing in preclinical and clinical trials.
Inhibition of RNAPII impairs DDR protein recruitment to DSBs. Representative time-lapse images of CtIP-GFP recruitment to DNA damage in RNAPII -inhibited (THZ1, 1 µM during 2 h) and DMSO as control during 600 s post microlaser irradiation in U2OS cells. n = 3 biologically independent experiments. (CREDIT: Nature Communications)
Despite these challenges, researchers remain optimistic about the potential of RNA-targeted therapies for cancer. With continued research and investment in this area, it is possible that we could one day see a revolution in cancer treatment that is based on the power of RNA.
Collaboration and Funding
The collaboration between the Biomedical Institute of Seville, the University of Seville, and the Danish Cancer Society has been a crucial factor in the success of this research. The team's multidisciplinary approach and the use of cutting-edge technology have enabled them to make significant strides in understanding the role of RNA in repairing human genetic material and preventing cancer mutations.
The study's co-author, Diana Aguilar-Morante, emphasized the importance of collaboration in advancing cancer research. "Collaboration is key to achieving breakthroughs in cancer research. By working together and pooling our resources, we can make progress much faster than we would working alone," she said.
In addition to collaboration, funding has also been a critical factor in the success of this research. The Government of Andalusia and the Spanish Association against Cancer (AECC) have provided financial support for the project, allowing the researchers to continue their work and move the project forward.
The AECC, a non-profit organization dedicated to fighting cancer, has played a vital role in supporting cancer research in Spain. Since its establishment in 1953, the AECC has invested over 2.5 billion euros in cancer research, making it the largest private funder of cancer research in the country.
"We are proud to support this important research and to help advance our understanding of cancer and its treatments. Our mission is to fund research that will lead to better outcomes for cancer patients, and we believe that this project has the potential to make a significant impact," said a spokesperson for the AECC.
The Government of Andalusia has also been a key supporter of cancer research in the region. The government has invested in the Biomedical Institute of Seville and other research institutions, providing resources and infrastructure to support their work.
In addition to these funding sources, the researchers have also received support from other organizations and institutions, including the European Union and the Spanish National Research Council (CSIC).
Moving forward, the researchers at the Biomedical Institute of Seville and the University of Seville plan to continue their work on RNA and cancer, with a particular focus on glioblastoma and paediatric neuroblastoma. Their goal is to improve the efficiency of RNA production inhibitors and reduce the side effects of cancer treatments, ultimately leading to better outcomes for cancer patients.
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Note: Materials provided above by University of Seville. Content may be edited for style and length.
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