More recently, large-scale sequencing efforts have identified genetic changes affecting JAKs in certain solid tumours. Missense mutations in JAK1 have been identified in 9% of patients with Hepatitis B-associated hepatocellular carcinoma, and validation in cell culture shows that these mutations increase phosphorylation of JAK1 and STAT3 and enable cytokine-independent growth. The evidence that the JAK/STAT pathway is activated in a large proportion of solid tumours and that its activation contributes to the malignant properties of cancer cells makes the JAK/STAT pathway a promising target for the development of new therapies. The effectiveness of targeting JAK/STAT signalling has been demonstrated in phase 3 trials in patients with PMF and myelofibrosis secondary to PV and ET. The JAK1/2 inhibitor ruxolitinib improves symptoms and prolongs survival.
Thomas S J, et al. The role of JAK/STAT signalling in the pathogenesis, prognosis and treatment of solid tumours[J]. British journal of cancer, 2015, 113(3): 365-371.