Scientists identify compounds that promise to block the 'Mount Everest' cancer gene

Only RNA can decide the fate of MYC 

According to the researchers, MYC is a transcription factor protein which means that it is directly involved in the maintenance of cancer stem cells in the body. These stem cells act as “seeds for cancer;” they initiate, proliferate, and provide treatment resistance to the tumors. These factors made the researchers realize that it is not feasible to target MYC at the protein level. 

However, they discovered that the messenger RNA which encodes MYC, forms structures that can work as potential targets. “We can target these structures via a small molecule that can furthermore be appended with compounds that can eliminate this mRNA,” said Disney. 

During their study, they found a total of 2,000 new RNA structures and six chemical structures that could bind to the MYC mRNA. They believe some of these structures could also prove to be effective against JUN and MIR155 genes. The former play an active role in lung cancer, breast cancer, glioblastoma, and 17 other types of cancers, whereas the latter causes the inflammatory reactions that drive cancer growth in humans.

Considering the complex and diverse structure of these genes, many scientists argue that drugs that target RNA may not work in their case. However, the authors of the current study believe that their RNA structures have the potential to change this belief. 

They suggest that RNA can be considered a small molecule drug target and compounds can be designed to eliminate mRNAs. This further implies that scientists can now target difficult proteins like MYC, and how they synergize at the mRNA level. 

“For cancer patients whose disease is driven by these common but challenging oncogenes, the RNA degrader approach may offer new hope,” said Herbert Waldmann, one of the study authors and director of the Max Planck Institute of Molecular Physiology.

RNA structures are not limited to cancer    

Disney and his team have been working on RNA structures for the last 15 years. They have come across numerous compounds that can target mRNAs. Also, when some of the previously identified structures were tested in mice, they eliminated cancer tumors. 

Moreover, they were also found to be effective against other medical conditions like myotonic dystrophy and amyotrophic lateral sclerosis (AML). “There are many targets we can apply this technology to and we are exploring very broadly the implications of this study across disease-causing RNAs,” Disney told IE. 

However, the RNA structures identified during the current study need further improvement before they are tested on animal models. He added, “The compounds are starting probes and not medicines. We need to do much to improve these compounds for use in mice and man.” 

The study is published in the journal Nature.