BTK inhibitors in the treatment of hematological malignancies and inflammatory diseases: mechanisms and clinical studies

Bruton's tyrosine kinase (BTK) is an essential component of multiple signaling pathways that regulate B cell and myeloid cell proliferation, survival, and functions, making it a promising therapeutic target for various B cell malignancies and inflammatory diseases. Five small molecule inhibitors have shown remarkable efficacy and have been approved to treat different types of hematological cancers, including ibrutinib, acalabrutinib, zanubrutinib, tirabrutinib, and orelabrutinib. The first-in-class agent, ibrutinib, has created a new era of chemotherapy-free treatment of B cell malignancies. Ibrutinib is so popular and became the fourth top-selling cancer drug worldwide in 2021. To reduce the off-target effects and overcome the acquired resistance of ibrutinib, significant efforts have been made in developing highly selective second- and third-generation BTK inhibitors and various combination approaches. Over the past few years, BTK inhibitors have also been repurposed for the treatment of inflammatory diseases. Promising data have been obtained from preclinical and early-phase clinical studies. In this review, we summarized current progress in applying BTK inhibitors in the treatment of hematological malignancies and inflammatory disorders, highlighting available results from clinical studies.

Automated summary

Bruton's tyrosine kinase (BTK) is a key component in regulating signaling pathways that affect B cell and myeloid cell functions, making it a promising target for treating B cell malignancies and inflammatory diseases. Several small molecule inhibitors have shown effectiveness in hematological cancers, and efforts are being made to develop more selective BTK inhibitors and combination approaches to overcome acquired resistance. Exciting progress has also been made in repurposing BTK inhibitors for treating inflammatory disorders. This review provides an overview of the current progress and clinical studies in using BTK inhibitors for hematological malignancies and inflammatory diseases.