Bruton’s Tyrosine Kinase Targeting in Multiple Myeloma

• Published in: International journal of molecular sciences Vol. 22; no. 11; p. 5707
• Main Authors: Von Suskil, Max, Sultana, Kazi Nasrin, Elbezanti, Weam Othman, Al-Odat, Omar S., Chitren, Robert, Tiwari, Amit K., Challagundla, Kishore B., Srivastava, Sandeep Kumar, Jonnalagadda, Subash C., Budak-Alpdogan, Tulin, Pandey, Manoj K.
• Format: Journal Article
• Language: English
• Published: MDPI 27-05-2021; MDPI AG
• Subjects: Bruton’s Tyrosine Kinase (BTK) inhibitors; drug development; microenvironment; multiple myeloma; resistance; Review
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms22115707

Multiple myeloma (MM), a clonal plasma cell disorder, disrupts the bones’ hematopoiesis and microenvironment homeostasis and ability to mediate an immune response against malignant clones. Despite prominent survival improvement with newer treatment modalities since the 2000s, MM is still considered a non-curable disease. Patients experience disease recurrence episodes with clonal evolution, and with each relapse disease comes back with a more aggressive phenotype. Bruton’s Tyrosine Kinase (BTK) has been a major target for B cell clonal disorders and its role in clonal plasma cell disorders is under active investigation. BTK is a cytosolic kinase which plays a major role in the immune system and its related malignancies. The BTK pathway has been shown to provide survival for malignant clone and multiple myeloma stem cells (MMSCs). BTK also regulates the malignant clones’ interaction with the bone marrow microenvironment. Hence, BTK inhibition is a promising therapeutic strategy for MM patients. In this review, the role of BTK and its signal transduction pathways are outlined in the context of MM.