Targeting BTK Signaling in the Microenvironment of Solid Tumors as a Feasible Cancer Therapy Option

SIMPLE SUMMARY: Protein tyrosine kinase BTK is essential for B cell maturation and proliferation. Dysregulation of BTK signaling in B cells leads to B cell lymphoma. In addition to B cells, BTK is also expressed in other types of immune cells including MDSC, dendritic cells, mast cells and macrophages, all of which comprise the tumor microenvironment in solid cancers. Although BTK inhibitors have been FDA-approved as the front-line treatment for B cell malignancy CLL/SLL, studies have been reluctant to report on BTKs role within the tumor microenvironment during solid cancer development limiting the possibility of using these BTK inhibitors as an adjuvant treatment option for solid cancers. Here, we review BTK signaling within the cells found in the tumor microenvironment as well as summarizing clinical trials using BTK inhibitors which target the tumor microenvironment in an attempt to combat solid tumors. ABSTRACT: The cell environment plays a pivotal role in determining cellular outcome, as well as cancer initiation, progression, and dissemination. Within this environment, in addition to the structural components, such as the extracellular matrix, there are various types of cells surrounding the tumor cells. Communication among these cells and the tumor cells via signaling pathways is important for tumor growth. Originally discovered in patients with immunodeficiency X-linked gammaglobulinemia, the Bruton’s tyrosine kinase (BTK) signaling pathway, known for its role in B cell maturation, is critical to cancer cell proliferation, metastasis and evasion of cancer eliminating cells. Given that BTK inhibitors have been FDA approved for chronic lymphocytic leukemia/small lymphocytic lymphoma and that the majority of BTK studies have been focused on B cells, the use of BTK inhibitors as a future treatment strategy of solid tumors has yet to be evaluated. In this review, we summarize studies analyzing BTK signaling within the cells found in the tumor microenvironment, as well as clinical trial where BTK inhibitors are currently being used to target the tumor microenvironment as a way to combat solid tumors.