Concurrent mutations are necessary for cancer initiation and progression. Most of the targeted anti cancer drugs were design to suppress the consequences of those mutations. However, cancer cells become resistance by acquiring novel mutations. A more promising approach is to identify and target non-mutated pathways that are redundant in normal cells but are required for the proliferation and survival of cancer cells.
Hyper-activation of Jak-STAT3 signalling is one of the hallmarks of a majority of gastrointestinal (GI) cancers. Attempts at developing specific inhibitors of STAT3 have so far proven challenging. However, a large portfolio of Jak kinase inhibitor drugs already exists for inflammatory diseases and haematological malignancies, we aim to repurpose these types of drugs for GI cancers. Targeting Jak1/2 was previously shown by our lab to be effective to reduce tumourigenesis in gastric and colon cancer. However, since Jak kinases have essensial roles in haematopoesis, targeting both Jak1 and 2 may cause some toxicity and side effects. Therefore here we aimed to identify the main Jak kinase that can be specifically targeted for the treatment of GI cancers.
By examining the effect of specific Jak inhibitors on colon cancer cells in vitro and in vivo and the roles of different members of Jak kinase family in gastric and colon tumourigenesis, we identified that Jak1 kinase is the main Jak kinase in tumorigenesis of GI cancers and could be a promising target for treatment of these types of cancers.