Venu Raman and his team are awaiting approval to begin human trials of their revolutionary new cancer drug RK-33

Venu Raman began his career in developmental biology, studying drosophila (fruit flies) and sea urchins. Improbably, that work would spark the development of one of the most promising potential cancer treatments in decades.

Raman was a postdoctoral student working on understanding the role of connective tissues during sea urchin embryogenesis when he began to consider the possible connection between developmental biology and cancer formation. Focusing on breast cancer, Raman noted that the breast goes through many developmental phases — first before birth, then at puberty, then lastly, during the childbearing years. How do the different generative phases of the breast contribute to the formation and progression of breast cancer? The drive to find out would bring Raman to Johns Hopkins, where he has been a professor and cancer researcher for over 20 years. He also leads a lab that combines developmental biology with molecular imaging to study tumor formation and progression.

Raman and his team were initially studying the effect of secondhand smoke on breast cancer formation and progression when they identified DDX3, an RNA helicase gene. The human DDX3 protein is a multifunctional protein implicated in various biological processes. While it was known that DDX3 played a role in the replication of viruses, its role in cancer biogenesis had not been well investigated.

After studying the gene functions in depth, Raman and his team realized that DDX3 also facilitates different types of tumor formation. They identified that suppressing the gene’s function slows or halts the growth of the tumor and reduces the metastatic burden. After replicating the findings, the team began working on a drug to target DDX3 specifically.

The team spent years working through various obstacles before successfully developing a drug, RK-33. This drug targets DDX3 by fitting into one of the gene’s protein pockets, thus nullifying its activity. When RK-33 halts DDX3 activity, specifically in cancer cells, it induces chaos and instability, leading to cancer cell death, while surrounding normal cells remain unaffected.

Excited by these results, the team started looking at lung cancer caused by cigarette smoking. Currently, the primary treatment is radiation. What would happen if they combined radiation with the RK-33 treatment? Surprisingly, a small amount of the drug and a small dose of radiation amplified each other’s effect, maximizing the impact while minimizing the toxicity associated with radiation. For the patient, this means more effective treatment with fewer side effects. Studies have shown RK-33 to be effective in treating many types of cancers, including cancers that have metastasized to other parts of the body.

Raman’s lab is working to treat some of the most aggressive forms of cancer, including brain cancers. Recently, Raman received a grant from the Ben and Catherine Ivy Foundation to support research into glioblastoma treatment. Raman and his team rely on support from donors to continue their groundbreaking work with RK-33. This funding is crucial in bringing this promising treatment from the bench to the bedside.

RK-33 is also an effective antiviral agent, showing promise in treating COVID-19 and other diseases.

Researchers have completed animal trials with RK-33, and are awaiting approval to start human trials. According to Raman, the lab is preparing an Investigational New Drug Application for the FDA. He noted that a preliminary application was well received; the complete package will be submitted in late 2024 or early 2025. With patients contacting him about the exciting new drug, he hopes to start human trials in 2025.