A research team has identified two new genes that might contribute to chemotherapy resistance in drugs used in liver cancer treatment.
A team of researchers led by Indian origin scientist from Virginia Commonwealth University Massey Cancer Centre has done the research.
Liver cancer is a highly aggressive form that has limited therapeutic options. One of the key challenges with cancer treatment is that patients can develop resistance to chemotherapy.
During the study, the researchers reported that two genes, astrocyte elevated gene-1, or AEG-1, and late SV40 factor, LSF, contribute to resistance of a commonly used chemotherapeutic drug called 5-fluorouracil, or 5-FU.
The team found that over-expression of AEG-1 increased resistance of the liver cells to 5-FU.
They observed that a second gene, LSF, is under the control of AEG-1 and mediates a series of molecular pathways involved the resistance to 5-FU.
Earlier this year, the team determined that AEG-1 modulates expression of genes relevant to the progression of liver cancer, including invasion, metastasis, resistance to chemotherapy, the formation of new blood vessels and senescence. They identified that LSF, a transcription factor that regulates gene expression, is increased by AEG-1.
"Since AEG-1 is a key regulator of liver cancer development and progression, understanding how this molecule works will provide profound insights into the mechanism of liver cancer development," said principal investigator Dr. Devanand Sarkar, a Harrison Endowed Scholar in Cancer Research at the VCU Massey Cancer Center and assistant professor in the Department of Human and Molecular Genetics in the VCU School of Medicine.
"By understanding these molecular pathways and mechanisms, we may be able to create new drugs to inhibit the expression of AEG-1 or LSF and even develop combination drug therapies to enhance the effectiveness of 5- fluorouracil," he added.
Sarkar said that AEG-1 contributes to resistance to not only 5-FU, but also to other chemotherapeutics such as doxorubicin and cisplatin, although the molecular mechanism of resistance to the latter drugs is different from 5-FU.
The study is in the Early Edition of the Proceedings of the National Academy of Sciences.