Michael Cain graduated from Curtin University WA in 1980 and since 1988 has held the post of Senior Pharmacist (Oncology) at Sir Charles Gairdner Hospital in Perth. He has been an invited lecturer at post-graduate and undergraduate level as well as being involved in numerous National training programs. He has published works and contributions to a number of texts and journals and has received State and National awards in recognition of his contributions to Oncology Pharmacy Practice.
The JAK/STAT pathway is essential link between cell surface cytokine/haematopoietin receptors and gene expression in haematopoietic cells governing immune balance. The Jak kinases (Jak1, Jak2, Jak3, and TYK) and related STAT molecules respond differentially to interleukins, interferons, erythropoietin, GM-CSF and other signals to play a pivotal role in orchestrating growth, differentiation, transformation and function of T-lymphocyte subsets.
Small molecule, selective Jak kinase inhibitors (jakanibs) have recently been developed and are providing new therapeutic options for diseases associated with dysregulated immune response, autoimmunity, and chronic inflammatory responses. Tofacitinib, an inhibitor of Jak1, 2 and 3, is approved for use in moderate-severe rheumatoid arthritis. Ruxolitinib, a Jak1 and 2 inhibitor, is available for myelofibrosis and for polycythaemia vera resistant to hydroxyurea treatment. Following this is a rapidly expanding body of evidence indicating that the jakanibs will be useful across a broad array of immunologically mediated pathologies including, ulcerative colitis, Chrohns disease, psoriasis, alopecia areata, atopic dermatitis, and vitiligo. Ruxolitinib was recently recognised for potential in the treatment of steroid resistant graft versus host disease.
There are significant toxicity concerns with tofacitinib and ruxolitinib. Myelosuppression and serious infection (including opportunistic infections) require close management and consideration. Mild changes in liver function tests and lipid changes are common. A withdrawal syndrome noted with ruxolitinib withdrawal or interruption can be severe in myelofibrosis patients. Potential malignancy risk with jakanibs remains to be fully characterised.