DNA methylation of drug transporter gene might explain chemoresistance in liver cancer

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Hepatocellular carcinoma is the third highest cause of cancer-related
death world-wide. Although several treatments are available – and many more are
undergoing clinical trials – drug resistance is a problem in some cases.

In the latest issue of Genome
Medicine
, Matthias Schwab and colleagues show for the first time
that there is a link between the level of expression of the chemotherapy drug
transporter SLC22A and DNA methylation. This finding  might explain reduced drug responses in liver
cancer and provide a new approach for treating patients.

The team looked at the methylation patterns in the 5′ end of
three genes encoding organic cation transporters (SLC22A1, SLC22A2 and SLC22A3)
in liver samples taken from people with hepatocellular carcinoma and compared
them with normal livers.  A
state-of-the-art mass spectrometry approach was used to examine DNA
methylation.

They found that decreased
expression of SLC22A1 in hepatocellular carcinoma correlated with increased
methylation of the SLC22A1 gene, and suggests that SLC22A1 is epigenetically
regulated.

The good news is
that epigenetic modifications are reversible and so pretreatment with a
chemical to reduce methylation might result in improved chemotherapy.