RK-33 May Be Significant in Treatment of Breast Cancer Bone Metastasis

A study published in Cancer Letters demonstrated new promise in the treatment of breast cancer bone metastasis, or breast cancer that has spread to the bone. The study showed that the drug RK-33 (Natsar Pharmaceuticals, John Hopkins Medicine)—which was previously shown to help treat other types of cancer and viral illnesses—can be an opportunity for this patient group whose disease can be incurable and whose limited treatment options are often focused on palliative care.¹

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The study findings build off previous work with RK-33, according to the authors. These results show that the protein DDX3 is inhibited and targeted by RK-33, which is found to be elevated in cancer cells. DDX3 is an RNA helicase, and its unwinding activity regulates various functions in tumor or cancer cells—including the facilitation of translating RNA’s genetic code into proteins—which promotes the growth of cancer cells and contributes to the spreading of the disease. High levels of DDX3, according to the authors, can be associated with poor overall survival and bone metastasis. RK-33 can slow down cancer progression by controlling the growth and proliferation of cancer cells.^1,2

“One of our main queries was whether RK-33 could be effective for treating bone metastasis, based on previous lab findings that showed its effectiveness in suppressing breast cancer growth,” said Johns Hopkins Kimmel Cancer Center member Venu Raman, PhD, professor of radiology, radiological science, and pharmacology at the Johns Hopkins University School of Medicine, in a news release. “We first had to determine whether DDX3 was expressed in patient samples of breast cancer bone metastasis, and we found DDX3 was expressed at high levels in these samples.”¹

For this study, the researchers tested mice if RK-33 had any effect on the DDX3 protein and the function of cancer cells. One group received placebo, whereas the other received RK-33. When looking at images, the mice who received RK-33 appeared to have all evidence of bone metastases eliminated by RK-33, and the treatment also preventing cancer cells within the bone from spreading to other organ systems. The mice who were treated with placebo did not present these effects. Further, the investigators note that even though this was demonstrated in mice, the findings indicate that RK-33 has the potential to fully eliminate breast cancer bone metastasis cells by stopping DDX3 and penetrating bone microenvironments that can often block other therapeutic options.^1,2

Further, RK-33 also demonstrated promise in preventing the occurrence of breast cancer bone metastasis. A group of mice that had breast cancer which had not yet spread to bone had also received the drug, and it was observed that the cancer never developed into bone metastases. Additionally, there were no significant adverse events related to RK-33 during the research’s duration.^1,2

Overall, the study is an indicator that DDX3 is a relevant clinical target within breast cancer bone metastasis and that RK-33 can be a safe and effective treatment for patients. Additionally, they urged for future research to investigate the drug’s ability to treat other conditions as well as the role of DDX3 within other diseases.^1,2

“This is a unique research opportunity because this is not the classical investigation into tumor suppressors or oncogenes,” said Raman in the news release. “We have demonstrated DDX3’s involvement in aggressive cancers and how RK-33 represents a significant advancement in utilizing targeted therapies for cancers that currently lack specific treatments.”¹

REFERENCES

1. John Hopkins Medicine. Experimental cancer drug eliminates bone metastases caused by breast cancer in lab models. News release. October 15, 2024. Accessed October 15, 2024. https://www.eurekalert.org/news-releases/1061208

2. Winnard PT, Vesuna F, Bol GM, et al. Targeting RNA helicase DDX3X with a small molecule inhibitor for breast cancer bone metastasis treatment. Cancer Lett. 2024;604:217260. doi:10.1016/j.canlet.2024.217260