Chinese scholars explore new drug treatment pathways for retinoblastoma

A research project jointly completed by Zhou Dan, director of the ophthalmology department of Suzhou High-tech Zone People's Hospital, and Fu Songbin, professor of medical genetics at Harbin Medical University, was recently published online in the latest issue of the internationally renowned journal Translational Medicine. For the first time, the researchers used ursolic acid, a natural compound derived from Chinese herbal medicine, to fight retinoblastoma, proving that this substance has good anti-cancer activity and can inhibit cancer cells at subtoxic doses, while being basically non-toxic to normal cells.

Retinoblastoma is a malignant tumor derived from photoreceptor precursor cells, and the origin cells are generally considered to be retinal stem cells or retinal precursor cells. This disease is more common in children under 3 years old, and most children are diagnosed in the first year or second year after birth, while adult cases are very rare. This disease has a familial tendency and can occur in one eye, one eye, or both eyes at the same time. It is the most common intraocular malignancy in infants and young children. The prevalence rate has no gender or racial differences. It can cause 1% of children to die from cancer and 5% of them to become blind in one or both eyes.

Director Zhou Dan introduced that clinically, retinoblastoma has complex manifestations and is difficult to detect in the early stages. After the tumor gradually grows, most children have yellow-white reflections in the pupil area, which is called leukocoria. Other symptoms include conjunctival and corneal congestion, edema, iris neovascularization, vitreous opacity, increased intraocular pressure, and strabismus. It is very easy to metastasize intracranially and to distant sites. Early detection, early diagnosis, and early treatment are undoubtedly the key to improving cure rates and reducing mortality rates. In the past few years, chemotherapy drugs such as carboplatin, vincristine, and etoposide combined with freezing, laser photocoagulation, and other methods have played a major role in the survival and visual function of children. If the disease enters the late stage, the chances of blindness and tumor recurrence will increase, and the ototoxicity caused by carboplatin will also cause serious damage to hearing. At the same time, patients are also at high risk of developing other cancers in their later years, such as bone cancer, brain cancer, and melanoma.

Zhou Dan, Director of Ophthalmology Department, Suzhou High-tech Zone People's Hospital

It is an indisputable fact that the existing treatment methods for retinoblastoma have adverse consequences both systemically and locally, thus limiting further clinical use of drugs. This urgently requires industry experts to identify new strategies, develop new retinoblastoma drugs and lock targets to improve the clinical efficacy of retinoblastoma patients. Chief Physician Zhou Dan's team and Professor Fu Songbin's research team closely targeted this hot topic in ophthalmology and deeply explored the tumor-suppressing mechanism of ursolic acid, a natural compound, on human retinoblastoma cells. Ursolic acid contains pentacyclic terpenoid compounds, which can be obtained from folk Chinese herbal medicine extracts and help protect cells from carcinogens.

Fu Songbin, Professor of Medical Genetics, Harbin Medical University

The results showed that subtoxic doses of ursolic acid not only regulated drug targets, but also effectively promoted the decrease in the level of phosphorylated protein kinase, the increase in the stable form of the p53 gene (human tumor suppressor gene), and the decrease in the phosphorylated double minute 2 gene, and also showed the key involvement of fatty acyl coenzymes. By reducing intracellular glutathione, the cytotoxicity of ursolic acid was significantly reduced, and the attack on retinoblastoma was enhanced.

Experts commented that the above research revealed for the first time the mechanism by which ursolic acid inhibits the growth of retinoblastoma, provided a new scientific basis for the targeted treatment of retinoblastoma, opened up new ideas and new horizons for humans to conquer the difficult and stubborn disease of retinoblastoma, and also expanded new areas for the development of the treasure house of traditional Chinese medicine.