New research indicates that paclitaxel suppresses tumours when given at a certain dosage, but at low doses, it actually promotes cancer spread to the liver.
Paclitaxel is the most commonly used chemotherapeutic agent in breast cancer treatment.
In addition to its well-known cytotoxic effects, recent studies have shown that paclitaxel has tumour-supportive activities.
Importantly, paclitaxel levels are not maintained at the effective concentration through one treatment cycle; rather, the concentration decreases during the cycle as a result of drug metabolism.
Using microarray analysis to investigate gene expression patterns in invasive breast cancer cells treated with low or clinically relevant high doses of paclitaxel, researchers from the Department of Immunology, Center for Human Disease Genomics, School of Basic Medical Science, Peking University Health Science Centre, Beijing, China investigated the effects of low doses of paclitaxel on cell migration, invasion and metastasis in vitro and in vivo.
The results, published in the FEBS Journal, show that low doses of paclitaxel seem to promote inflammation and initiate the epithelial–mesenchymal transition, which the team noted to enhance tumour cell migration and invasion.
Furthermore, low doses of paclitaxel promoted liver metastasis in mouse xenografts, which correlated with changes in estrogen metabolism in the host liver.
Collectively, these findings reveal the paradoxical and dose-dependent effects of paclitaxel on breast cancer cell activity, and suggest that increased consideration be given to potential adverse effects associated with low concentrations of paclitaxel during treatment.
The findings suggest that lowering the dose of paclitaxel to reduce toxic side-effects is not a safe strategy.
“Paclitaxel and its analogous compounds are the first line agents widely used in clinical cancer chemotherapy. However, potential risks and reasonable treatment strategies of paclitaxel continue to be widely investigated,” wrote the authors.
[hr] Paper: The FEBS Journal