Targeting Bruton Tyrosine Kinase

Bruton tyrosine kinase (BTK) was originally discovered over twenty years ago as defective in X-linked agammaglobulinemia: a heritable disorder characterized by a near complete block in B cell differentiation. BTK was subsequently recognized as an essential protein for the signaling triggered by the engagement of the B-cell receptor, as well as Fc and Toll-like receptors. In fact, BTK plays pivotal roles in B cell proliferation, maturation and survival and it is therefore involved in many pathologies characterized by a defective or abnormal B-cell physiology, such as auto-immune diseases and B-cell leukemia/lymphomas. For this reason, biotech and pharmaceutical companies have focused on developing BTK inhibitors over the last decade leading to fast-track approval by the FDA for three drugs currently in the clinic, and sixteen others in clinical trial. Recent research has expanded our understanding of BTK expression as BTK isoforms have been discovered in solid tumors creating new opportunities to target this protein for therapeutic benefit.

The objective of this Research Topic is to provide a comprehensive overview of the roles of BTK isoforms in normal and tumoral bone-derived cells, as well as in solid tumors. We will also explore the potential benefit of targeting BTK and its isoforms in the increasing number of pathologies characterized by increased or dysregulated BTK activity. We aim to highlight the state-of-the-art in the BTK field and suggest novel hypotheses/ideas that can be harnessed to better understand how BTK is involved in different pathologies and drive further development of BTK as drug target.

We welcome Original Research, Reviews, and Mini-Review articles focusing on, but not limited to, the following topics:
• BTK in innate and acquired immunity
• BTK in auto-immunity and allergies
• BTK in inflammatory-related pathologies
• BTK in platelets
• BTK in B-cell malignancies
• BTK inhibitors, past experiences and future approaches
• BTK in solid tumors