Time‐dependent changes in proliferation, DNA damage and clock gene expression in hepatocellular carcinoma and healthy liver of a transgenic mouse model

What is it about?

HCC is highly resistant to antimitotic therapies. Introducing the concept of chronotherapy in HCC treatment may improve the efficacy of antimitotic therapy and reduce its severe side effects. To evaluate any beneficial effect of antimitotic therapies on the HCC, it is necessary to clarify whether cell proliferation and DNA repair mechanisms in HCC cells follow a daily pattern and whether this pattern differs from that in the surrounding healthy liver (HL) tissue. These questions are addressed in the present article.

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Why is it important?

The acquisition of therapeutic resistance in hepatocellular carcinoma (HCC) is a major obstacle in chemotherapy-based approaches to HCC treatment. Therapeutic resistance may be attributed in part to the phase of tumor development at the time of therapy. Here, assessment of timing of antimitotic therapies in an HCC animal model reveals time-of-day dependent changes in tumor cell proliferation and DNA damage. In addition, clock gene expression was altered in HCC, suggesting a link to tumor development and growth. The results indicate that the efficacy of antimitotic therapies depends on proper timing and that this time dependency should be evaluated further.