HMN 2026: How ‘Molecular eraser’ destroys cancerous mRNA before protein forms, reshaping cancer cells

Many of the deadliest forms of cancer are caused by a pathological mutation in the RAS protein. Yet, to date, no effective treatment for this cancer protein has been found. A new research approach aims to prevent the protein from forming in the first place by destroying its blueprint—the mRNA. Based on this strategy, the research group led by Peng Wu at the Max Planck Institute of Molecular Physiology has now developed a new type of “molecular eraser” targeting the mRNA of the cancer protein NRAS. Their findings are published in JACS Au.

The RAS protein is pathologically altered in a wide range of cancers: It causes about 40% of colorectal cancer cases and more than 90% of pancreatic cancer cases, the deadliest of all cancers. A new drug targeting RAS would be a real game changer for cancer therapy. However, RAS was long considered undruggable because it is very difficult to target using common pharmaceutical approaches. And although the first RAS drug for the treatment of lung cancer was approved in 2021, the development of further drugs remains complex and costly. New, alternative strategies could provide a solution.

Cancer RNA on the hook

An American research team, in collaboration with MPI researchers in Dortmund, recently developed a promising alternative approach to cancer therapy.

The concept behind it is ingenious: Instead of disabling the cancer protein itself, its production is halted. This is achieved using a specially designed chimeric molecule (RIBOTAC), which binds to the pathogenic RNA at one end and has a chemical “hook” at the other. This hook captures RNA-degrading enzymes, which break down the bound RNA and thus prevent production of the protein.

Unexpected results

Based on this new concept, Wu’s team has now developed a new RIBOTAC targeting the mRNA of the cancer protein NRAS. Although the RIBOTAC was shown to degrade the mRNA, the researchers could not detect any significant difference in the total amount of the protein. They suspect that only a subform of NRAS, present in small quantities, was eliminated.

But this is precisely where the surprise came: Despite the minimal impact on the total protein quantity, the treated cancer cells changed their appearance dramatically.

Fundamental dogma of drug research called into question

“The molecules left a biological fingerprint that does not match any known class of active substances,” explains Wu. “This suggests that we are targeting entirely new signaling pathways or mechanisms.”

With their findings, the researchers are challenging a fundamental dogma of drug research: Until now, it was assumed that a therapeutic effect could be achieved only if a significant proportion of the target RNA or protein was affected (e.g. inhibition, activation or degradation). In this study, however, the removal of even a tiny fraction of RNA (

In the future, the team plans to decipher the mechanisms influenced by the RIBOTAC and investigate how this influence affects cancer cells. At the same time, the chemistry and binding strategy will be further optimized to produce improved next-generation “molecular erasers.”

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