AEG-1 and LSF are suspected to hinder treatment with 5-FU, according to a study in PNAS.

Two genes may contribute to resistance to 5-fluorouracil (5-FU) chemotherapy in liver cancer patients, according to Virginia Commonwealth University (VCU) Massey Cancer Center researchers. The genes are called astrocyte elevated gene-1 (AEG-1) and late SV40 factor (LSF), as reported in a study published online in the July 13 early edition of the Proceedings of the National Academy of Sciences.

The team found that overexpression of AEG-1 increased resistance of the liver to 5-FU. They also observed that LSF is under the control of AEG-1 and mediates a series of molecular pathways involved with 5-FU resistance. 

Previous studies found that the expression of AEG-1 was very low in normal cells or tissues such as breast, prostate, liver, and brain. In cancers of the same organs, however, AEG-1 expression was significantly increased. 

The VCU 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.

The researchers say 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 team is currently conducting studies to further understand the molecular mechanisms by which AEG-1 induces resistance to chemotherapy. Additionally, novel combinatorial treatment approaches that incorporate AEG-1 or LSF inhibition in a standard chemotherapeutic protocol will be evaluated for their efficacy in inhibiting liver cancer in animal models.

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