Publications

Janus kinases (JAKs) mediate the regulation of a variety of cytokine signals with alterations in JAK1, JAK2, JAK3 and Tyk2 signalling contributing to many disease states including autoimmune diseases and haematological malignancies. Recently tofacitinib and ruxolitinib have been approved for treatment for rheumatoid arthritis and myelofibrosis respectively. Several JAK2 inhibitors, such as momelotinib and pacritinib, currently in development for myelofibrosis and the JAK1/2 inhibitor baricitinib is in development for RA and psoriasis. Despite these advances, JAK inhibition appears to be limited in its ability to induce remission in haematological malignancies and, with chronic use, a resistance is built, possibly due to the acquisition of secondary mutations. In these cases alternative methods of targeting JAKs, such as type 2 inhibition or HSP90 inhibition, or the use of combined pathway inhibition to block STAT, PI3K/Akt and MAPK etc. could be critical in the treatment of malignancies.