Primary liver cancer, which consists predominantly of hepatocellular carcinoma (HCC), is the fifth most common cancer worldwide and the third most common cause of cancer mortality. Primary liver cancer, which consists predominantly of hepatocellular carcinoma (HCC), is the fifth most common cancer worldwide and the third most common cause of cancer mortality.
The absence of compelling remedial mediations for HCC has additionally made liver cancer the following leading reason for cancer death around the world. Current medications, for example, sorafenib and regorafenib, used to treat HCC are not durable, and usually are just used to treat patients with advancing stage HCC.
Now, scientists at the Cancer Science Institute of Singapore (CSI Singapore) at the National University of Singapore, and the Agency for Science, Technology, and Research (A*STAR)’s Genome Institute of Singapore (GIS) have discovered four potential drug compounds that target hepatocellular carcinoma (HCC). Scientists found these drugs using a cancer gene-targeting drug-screening platform.
The cancer gene-targeting drug-screening platform is tapped on libraries of synthetic molecules and natural compounds to detect potential drug candidates against SALL4, a cancer gene linked to HCC. These drug candidates can address the unmet medical need for more effective treatments of HCC.
Four natural compounds were found to be targetting SALL4. Moreover, these natural compounds could potentially limit SALL4-linked HCC cancer cell growth. Detail investigation on these compounds suggests that they are inhibitors of oxidative phosphorylation, a metabolic pathway that promotes the growth of cancer cells with high SALL4 expression.
The group additionally exhibited that the most potent natural compound distinguished, oligomycin, had higher efficiency than existing standard-of-care drug sorafenib in preclinical studies and showed little toxicity at effective doses. Streptomyces bacteria deliver oligomycin. At the point when joined with sorafenib, oligomycin could additionally decrease the growth of SALL4-linked HCC tumors in vivo.
Dr. Justin Tan, CSI Honorary Research Fellow, and GIS Innovation Fellow, who led the study, said, “Our study has identified a vulnerability in tumors that express cancer gene SALL4, as well as compounds targeting this vulnerability. These compounds have great potential to be further developed into drugs to effectively treat liver cancer and other cancers linked to this gene. Further studies on these compounds can lend deeper insights to bring advancement to precision medicine for SALL4-linked cancers, and to improve the quality of cancer treatments.”
Prof Patrick Tan, Executive Director of GIS and Senior Principal Investigator at CSI, said, “Liver cancer is the sixth most common cancer worldwide, affecting about 24 individuals in every 100,000 people a year. Hence, the current lack of therapeutic options for it is a grave concern. With the development of the drug-screening platform, this study aims to address that concern by providing a more efficient drug discovery process. Also, their discovery of potential drug compounds could pave the way for more effective and personalized liver cancer treatments in the future.”
Scientists are further planning to develop the oxidative phosphorylation inhibitors discovered for clinical testing in cancer patients, with the hope of bringing a more effective treatment option to patients with SALL4-linked cancers. The team also aims to expand its innovative drug-screening platform to discover drugs that target other cancer genes in different cancer types.