Verifying the therapeutic potential of newly discovered siRNA drug candidates for treating acute leukemia.

Leukemia, a type of blood cancer, kills about 350000 people annually. Existing treatments are often aggressive and particularly affect children and the elderly. There is therefore a strong need for more targeted, gentler therapies. Researchers at NTNU study an enzyme involved in inflammation that helps cancer cells survive. The idea behind the project is that by creating targeted treatment against this enzyme, cancer cell death can be initiated without affecting healthy cells. Treatment can be designed in different ways; either by directly blocking the enzyme itself or by targeting the RNA that produces the enzyme. They previously showed that directly inhibiting the enzyme caused leukemia cells to die. In this project, the researchers tested a potential new RNA-based drug. The most promising candidates were selected based on strong reduction of the target enzyme and minimal unintended effects, and a PCT patent application was submitted supported by the project results. The team has also looked at the market, spoke with several actors, and developed a commercialization strategy. Early testing of the RNA-based drug candidates showed a successful reduction of the enzyme in leukemia cells, but this did not lead to cancer cell death. The researchers will continue to investigate why different molecular approaches targeting the same enzyme result in different biological outcomes and to explore the therapeutic potential of RNA-based targeting of this enzyme to treat other diseases.

The team confirmed that the drug candidates were able to reduce the levels of the intended target protein in leukemia cells. However, this reduction did not lead to the expected therapeutic benefit. These findings provided valuable learning for the entire team about the unpredictable nature of biology and the challenges involved in developing RNA-based medicines. Our results also highlight the need for caution when interpreting results from traditional inhibitor studies, as their effects may not fully reflect how RNA-based drugs will behave. Overall, the project generated important insights that will inform future research, and we are very grateful to the Research Council of Norway (RCN) for funding this work.