Genes Key to Mesothelioma Chemotherapy Response

Research being performed in Eastern Europe may eventually help doctors around the world predict which mesothelioma patients will respond best to a particular type of chemotherapy.Genes Key to Mesothelioma Chemotherapy Response

Mesothelioma is a fast-growing cancer triggered by exposure to asbestos.  It is often treated with multiple modalities, including chemotherapy.  As more is understood about the impact of genetics on medication response, chemotherapy for cancers like mesothelioma is moving away from a “one-size-fits-all” approach to a more tailored approach based on individual cellular characteristics.

Now, a team of biochemists in Slovenia are studying genetically-linked responses to the chemotherapy drug gemcitabine, a nucleoside analog that some studies have found to be a promising alternative to the more conventional cisplatin-pemetrexed combination for mesothelioma.  In a phase II trial involving 78 mesothelioma patients treated with gemcitabine, half showed a complete or partial response to the drug.  But others had little or no response or experienced serious side effects.  In four cases, the mesothelioma spread while the patient was on gemcitabine.

To determine why some mesothelioma cases respond well to gemcitabine and others do not, the Slovenian team tested the cells of another 107 mesothelioma patients treated with a gemcitabine-platinum mix.  Cell samples were tested for 11 different polymorphisms or genetic anomalies as well as haplotypes (particular combinations of DNA sequencing) that might influence response to gemcitabine.

Of the different genetic arrangements studied, two had no influence on treatment outcomes, one appeared to significantly decrease overall survival probability, two decreased the odds of experiencing nausea and vomiting and others were associated with better or worse tumor responses.

In a summary of their results, the Slovenian team concluded that, polymorphisms and haplotypes do appear to influence the efficacy and toxicity of gemcitabine and “should be validated as potential markers for the prediction of clinical outcome in patients with malignant mesothelioma.”

If further studies support the findings, doctors may eventually be able to test for gemcitabine compatibility and take some of the guesswork out of mesothelioma treatment selection.



Erculj, N et al, “The influence of gemcitabine pathway polymorphisms on treatment outcome in patients with malignant mesothelioma”, November 29, 2011, Pharmacogenetics and Genomics, Epub ahead of print.
Kovac, V et all, “A phase II trial of low-dose gemcitabine in a prolonged infusion and cisplatin for malignant pleural mesothelioma”, October 24, 2011, Anticancer Drugs, Epub ahead of print.

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