Methotrexate Demonstrates Potential for Treating Rare Blood Cancer

Anti-rheumatic drug suppresses activation of a molecular pathway responsible for the disease.

Polycythemia Vera (PV) is a type of blood cancer that causes an overproduction of red blood cells. Symptoms include itchiness, headaches, weight loss, fatigue, and night sweats. Current treatment options do not slow disease progression and provide little symptom relief.

Now, scientists have discovered methotrexate (MTX)—–commonly used to treat inflammatory diseases––directly inhibits the molecular pathway responsible for causing PV.

For a study published in Haematologica, investigators conducted tests on fruit fly cells to screen for small molecules that modulate JAK/STAT signaling. Misregulation in this signaling pathway is central to the development of myeloproliferative neoplasms (MPNs), a collective term for progressive blood cancers, such as PV.

Next, testing was conducted in human cells. The results of the study showed MTX acted as a potent suppressor of JAK/STAT pathway activation

The latest mice tests were consistent with the cell-based studies, investigator Dr Martin Zeidler noted.

The use of low-dose MTX suppresses JAK/STAT pathway activity and normalizes raised blood counts and an increase in spleen size, which is associated with PV.

“We have now shown pretty conclusively that we can use this approach to treat mouse models of human MPNs, results which provide a much more tangible prospect of success in humans,” Dr Zeidler said. “Repurposing MTX has the potential to provide a new, molecularly targeted treatment for MPN patients within a budget accessible to health care systems throughout the world—–a development that may ultimately provide substantial clinical and health economic benefits.”

MTX has been on the market for more than 30 years to treat inflammatory diseases. The investigators hope to conduct a full clinical trial of their findings by early next year.