In many different cancers the cellular pathway JAK/STAT is activated. Thus, the pathway is an attractive therapeutic target, especially for malignancies of the bone marrow called myeloproliferative neoplasms (MPNs). Pharmacological JAK inhibitors, such as ruxolitinib, are available but are expensive and are often associated with side effects.
Now, a screening study in fruit-fly cells has identified two existing drugs — the anti-inflammatory and chemotherapeutic drug methotrexate and the closely related drug aminopterin — as potent suppressors of JAK/STAT activation.
“These effects occurred at drug concentrations already routinely prescribed for rheumatoid arthritis patients,” the authors report in PLoS One (online, 1 July 2015)
. “We suggest that patients with JAK/STAT-associated haematological malignancies may benefit from low-dose methotrexate treatments.”
Noting that methotrexate is a low-cost and well-characterised drug, the researchers will now undertake clinical trials of methotrexate as a therapy in MPNs and other haematological malignancies.