A study published in Neuro-Oncology, the collaborative research group between Hokkaido University, FUJIFILM Corporation and the National Institute of Advanced Industrial Science and Technology (AIST) sees hope in treating tumours with low toxicity as a compound which can kill chemotherapy-resistant cells called glioblastoma has been invented, as per reports. Until now, patients with glioblastoma had reportedly a poor prognosis despite all available treatments. Doctors say that that glioblastoma is a malignant glioma that can survive for up to 15 months in the human body. As there were no methods to eradicate glioblastoma-initiating cells (GICs) that demonstrate tumorigenicity (ability to form tumours) and resistance to chemotherapies and radiotherapies, the threats to cancer patients could not be averted earlier.
The study cites to have successfully cultured human GICs resistant to temozolomide (TMZ), a standard drug used for treating glioblastoma. As mentioned in the research paper, researchers used Fujifilm's compound library to conduct a high-throughput drug screening to identify a compound that can specifically kill or inflict damage to GICs. Candidate compounds were examined using cytotoxic activities, expressions of various cell markers, and tumour-suppressive activities as indicators in the process. Finally, the scientists zeroed down to Compound 10580 for being capable of killing or inflicting damages to GICs. The researchers observed that in order to do so, the compound inhibited the activity of dihydroorotate dehydrogenase (DHODH), an essential enzyme for pyrimidine synthesis found in the mitochondria's inner membrane. Further analysis also revealed that the compound decreased the expression of stem cell factors in GICs, unravelling a part of its molecular mechanism. The experiment was administered on lab mice with tumours.
Toru Kondo of Hokkaido University's Institute for Genetic Medicine, who led the study, said, "Compound 10580 is a promising candidate for developing drugs against glioblastoma and other recurring cancers. Further technological developments of a drug delivery system or 10580 derivatives, which can cross the blood-brain barrier, are needed."