Can pemetrexed’s (Alimta) effectiveness in mesothelioma treatment be improved?

In 2004, over 14 years ago (!) the FDA approved the first ever (and the last so far) mesothelioma treatment drug – Alimta (pemetrexed) in combination with cisplatin. The treatment is now very much considered standard and for some patients the results are dramatic. Unfortunately, patients and physicians alike are well aware of its limitations. For instance, the treatment is not effective for all patients, and some patients who do respond, have shorter overall survival than others.

The good news is that researchers are already working to understand the process behind why this treatment is effective for some and not others, and they’re also looking for solutions.

Dr. Elisa Giovannetti, an associate professor and clinical pharmacologist at VU University Medical Center in Amsterdam, Netherlands, is one of those researchers. Funded by the Mesothelioma Applied Research Foundation, Dr. Giovannetti and her team sought to understand pemetrexed (Alimta) resistance in order to answer the broader question of why malignant mesothelioma cells become chemo-resistant.  The results of their study were published in the prestigious Annals of Oncology journal.

“These findings identify for the first time PCFT (a protein) as a novel mesothelioma prognostic biomarker, prompting prospective trials for its validation,” Dr. Giovannetti concluded in her study.

Dr. Giovannetti and her team also add that preclinical data suggest that targeting PCFT-promoter methylation might eradicate pemetrexed-resistant cells characterized by low-PCFT expression. In lay terms, this means that they not only identified a new biomarker that can help predict pemetrexed’s effectiveness, but they have also suggested a way to overcome such chemo-resistance.

“Ultimately, ongoing validation studies on the key role of PCFT will be an important step forward to select patients for optimal treatment strategies,” added Dr. Giovannetti when asked about the future of this research.

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