Mesothelioma FGFR1 Gene Therapy Might Not Work After All

Researchers recently threw cold water on the idea that a gene present in mesothelioma patients might make a good target for treatment by using lab-modified tyrosine kinases inhibitors.

It has been thought — and hoped — that the gene FGFR1 might be a suitable place to launch a molecular attack once mesothelioma cells start massing. FGFR1 stands for fibroblast growth factor 1.

Tyrosine kinases inhibitors — TKIs, for short — seemed like they might make promising weapons against mesothelioma via FGFR1.

But the research reveals that TKIs appear incapable of affecting the inner workings of FGFR1.

The research was conducted by scientists at the University Medical Center in Köln, Germany. Their findings were published in the August 19 online edition of the journal BMC Research Notes.

“Our findings may be a hint that TKIs will not satisfy the hope for a new era in the treatment of malignant pleural mesothelioma,” they wrote.

The FGFR1-Mesothelioma Connection

The role of FGFR1 in mesothelioma is unclear.

The reason FGFR1 was considered a potential molecular target is that scientists have long been aware of a gene distantly related to FGRF1 that develops mutations mesothelioma finds helpful.

The related gene is epidermal growth factor receptor, or EGFR.

Notable about EGFR is that  when mesothelioma mutates it, EGFR overexpresses itself and, by extension, the receptor tyrosine kinases along its body.

Those receptor tyrosine kinases like to roll out the welcome mat for TKIs. This allows the TKIs to plug into the EGFR and upload substances capable of disrupting the gene’s internal operations.

This disruption could theoretically slow or stop mesothelioma from growing and spreading. So scientists have developed TKIs specifically for EGFR.

However, EGFR overexpressions in mesothelioma patients are extremely rare. Consequently, EGFR makes a poor molecular target.

FGFR1, on the other hand, makes for a much better target because it tends to be more abundant than EGFR.

But the problem the German researchers have now discovered is that FGFR1 doesn’t appear to overexpress itself.

And because it doesn’t overexpress itself, it doesn’t have sufficient receptor tyrosine kinases for the TKIs to plug into and cause havoc.

Mesothelioma Study Cohort Described

To conduct their research, the German scientists looked at the case histories of 19 pleural mesothelioma patients they had treated between 2008 and 2010.

The patients had been diagnosed with the disease by thoracoscopic examination and in accordance with World Health Organization evaluation criteria.

The mean age of the patients was 68. The majority of them knew that they had been exposed to asbestos earlier in life.

The researchers said the patients they enrolled in this cadre were selected because they had not received any chemotherapy and mesothelioma was the only cancer they had ever suffered.

Of these patients, 13 had the epithelioid type of mesothelioma. Epithelioid is the most responsive to treatment.

Five of the patients had the biphasic type. One had the sarcomatoid type, which is the least responsive to treatment.

During treatment, tissue samples were taken from the patients and thoroughly analyzed.

Although the study may dash hopes for FGFR1, the researchers concluded that investigation of receptor tyrosine kinases in other genes that might make suitable treatment targets should be conducted.