Bruton’s Tyrosine Kinase Signaling and Advancement in Multiple Myeloma Therapy

Author(s):  
Krishne Gowda ◽  
Max Von Suskil ◽  
Omar Al-Adat ◽  
Jennifer Dang ◽  
Kuntal Bhowmick ◽  
...  
2013 ◽  
Author(s):  
Destinee Bushman ◽  
Jared J. Bearss ◽  
Venkataswamy Sorna ◽  
Hariprasad Vankayalapati ◽  
Sunil Sharma ◽  
...  

2021 ◽  
Vol 22 (11) ◽  
pp. 5707
Author(s):  
Max Von Suskil ◽  
Kazi Nasrin Sultana ◽  
Weam Othman Elbezanti ◽  
Omar S. Al-Odat ◽  
Robert Chitren ◽  
...  

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.


2017 ◽  
Vol 53 ◽  
pp. 31-42 ◽  
Author(s):  
Manoj K. Pandey ◽  
Krishne Gowda ◽  
Shen-shu Sung ◽  
Thomas Abraham ◽  
Tulin Budak-Alpdogan ◽  
...  

2019 ◽  
Vol 2 (1) ◽  
Author(s):  
Sze-Ting Bong ◽  
Lydia Ngiik-Shiew Law ◽  
Jodi Woan-Fei Law

Multiple myeloma (MM) is characterized by the over-production of monoclonal plasma cells that eventually become malignant in the bone marrow. MM remains as an incurable cancer, but it can be treated through chemotherapy. Nonetheless, research on novel therapies for effective treatment of MM is ongoing and in this case the involvement of Bruton’s tyrosine kinase (Btk) in B-cell malignancies has made it one of the new therapeutic targets. In MM patients, it has been reported that the expression of Btk was elevated and this could potentially contribute to chemoresistance indirectly via enhancement of cell proliferation and survival. Ibrutinib is a highly selective irreversible Btk inhibitor commonly used as treatment for B-cell malignancies such as Mantle Cell Lymphoma (MCL) and Chronic Lymphocytic Leukemia (CLL). With reference to the potential involvement of Btk in MM and current treatment of MCL and CLL using ibrutinib, researchers have begun to examine the effect of ibrutinib treatment on MM. This review provides information on the association of MM and Btk in conjunction with the treatment using ibrutinib. To date, clinical trials of ibrutinib as therapeutic alternative for MM have produced promising results, particularly as combination therapy with other agents such as dexamethasone and carfilzomib. However, there is limited evidence on the Btk mechanisms involved in MM, hence, it is important to further investigate the Btk oncogenic signalling pathway(s) in MM cells in order to establish successful and improved treatment of MM.


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