New research has shown that liver cancer, a growing health challenge often diagnosed in its advanced stages, can be prevented by changing the metabolic programming of cells as a target therapy.

The research, conducted over six years, is a collaborative effort of scientists from CSIR-Central Drug Research Institute (CSIR-CDRI), Central Institute of Medicinal and Aromatic Plants (CIMAP), and Centre of Biomedical Research (CBMR), SGPGIMS, Lucknow.

Led by CDRI scientist Madhav Nilakanth Mugale, the research concludes that cancer cells change metabolic programming, and it can be used as a diagnostic tool for cancer prevention.

The research, published in the renowned international journal Elsevier, also unravels crucial insights into the metabolic mysteries behind Hepatocellular Carcinoma (HCC), a challenging form of liver cancer.

Besides delving into the intricacies of HCC, the research opens avenues for targeted therapies.

In their research work, CDRI’s Mugale and his team utilised an experimental model of HCC induced by a substance called Diethylnitrosamine (DEN), mirroring the development of the disease in humans.

The study revealed changes like decreased body weight, higher levels of certain enzymes in the blood, and alterations in the liver structure observed through special staining and microscopy techniques during the progression of HCC.

“Our team used advanced techniques like Immunohistochemistry (IHC) to identify elevated levels of specific markers in the cancerous liver, providing insights into the enhanced cancer-causing potential. They also delved into the role of a signalling pathway called STAT3-NFKB, uncovering its impact on the cell’s metabolism, which was found to be a key driver in the malfunction of mitochondria and reduced cell death,” said Mugale.

He said that an advanced technique called Nuclear Magnetic Resonance (NMR) is employed to analyse the metabolism of the liver cells and blood cells in a highly growing stage.

This revealed abnormal changes in the cell cycle, including energy formation and utilisation, such as the accumulation of a substance called succinate in the liver tissue, increased breakdown of ketones, and alterations in how the body processes amino acids in advanced stages of HCC.

Importantly, these metabolic changes in cells were found to closely align with the progression of liver cancer, potentially serving as early indicators of the upcoming disease.

“These findings bring hope for more effective interventions in the battle against liver cancer,” said CDRI director Radha Rangarajan.