Janus kinase inhibitors - holistically seeing two faces

Editor, - I was interested to read the recent article on Janus kinase inhibitors by Paul Kubler (Aust Prescr 2014;37:154-7). In addition to being pro-cancer, the Janus kinase-Signal Transducer and Activation of Transcription (JAK-STAT) pathway is part of a central physiological pro-survival mechanism.1 Thus pharmacological targeting of this signalling cascade may pose potential threats, for example to cardiac integrity.2 Targeting JAK-STAT will also potentially challenge neuroprotection.3 Conversely, activation of JAK-STAT is proposed as a tangible approach to managing heart disease.4 The message is that there is a clinically highly relevant ‘crossroads’ between physiology and cancer, thus maintaining the truly holistic viewpoint. Therefore treatments aimed at targeting cancer necessarily target normal tissues and in turn define burgeoning fields within cancer-related therapy such as cardio-oncology. Activating a pro-survival pathway such as JAK-STAT therapeutically to manage heart disease removes a barrier in the multiple-step process of oncogenesis. Targeting the JAK-STAT pathway is in a sense ‘non-specifically specific’. The target may be a defined one, but the target itself is universally expressed. Future developments in therapeutics must be designed to be ‘specifically specific’ to the disease target to be effective, yet with little fear of resultant adverse reaction.