New research shows drug used for arthritis can treat blood cancer


A new study funded by the UK Medical Research Council (MRC) has revealed that the arthritis drug methotrexate (MTX) can be used to treat patients with a type of blood cancer, polycythemia vera (PV).

PV results in an overproduction of red blood cells that causes itching, headaches, weight loss, fatigue and night sweats.

The research has been conducted by Dr Martin Zeidler, from the Department of Biomedical Science at England’s University of Sheffield, in collaboration with scientists from the Royal Hallamshire Hospital’s Department of Haematology.

Methotrexate is a drug included on the World Health Organisation’s list of essential medicines and is commonly used for the treatment of patients with rheumatoid arthritis, Crohn’s disease or psoriasis.

The initial tests were conducted on fruit fly cells to screen for small molecules that modulate JAK / STAT signalling.

JAK / STAT is a signalling pathway whose misregulation is the major cause for the development of myeloproliferative neoplasms (MPNs), the collective term for progressive blood cancers such as PV, in humans.

"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."

Further tests conducted on human cells demonstrated that the drug acts as a potent suppressor of JAK / STAT pathway activation, even in cells carrying the mutated gene responsible for MPNs in patients.

The tests revealed that low-dose MTX suppresses JAK / STAT pathway activity and can normalise both the raised blood counts and the increase in spleen size associated with the disease in the mouse models.

Zeidler said: “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.

“Repurposing MTX has the potential to provide a new, molecularly targeted treatment for MPN patients within a budget accessible to healthcare systems throughout the world, a development that may ultimately provide substantial clinical and health economic benefits.”


Image: An in silico model of the potential interaction between methotrexate and the JAK2 kinase domain. Photo: courtesy of The University of Sheffield.