TY - JOUR
T1 - Protein kinases
T2 - Emerging therapeutic targets in chronic lymphocytic leukemia
AU - Balakrishnan, Kumudha
AU - Gandhi, Varsha
N1 - Funding Information:
This work was supported in part by grants Lymphoma SPORE CA136411 and CLL PO1 CA81534 from the National Cancer Institute, Department of Health and Human Services and a CLL Global Research Foundation award, and a Global Research Foundation European Alliance award. The authors have no other competing interests to declare.
PY - 2012/4
Y1 - 2012/4
N2 - Introduction : Although protein kinases are primary targets for inhibition in hematological malignancies, until recently their contribution to chronic lymphocytic leukemia (CLL) was poorly understood. Insights into B-cell receptor signaling and its role in regulating key cellular functions have shed light on candidate protein kinases that are aberrantly activated in CLL. In this regard, protein kinases are now considered as potential drug targets in CLL. Area covered : This review has covered signaling pathways and associated protein kinases in CLL and the kinase inhibitors currently available in preclinical and clinical investigations. Individual protein kinases that are abnormally active in CLL and the functional consequences of their inhibition are discussed. Expert opinion : A growing body of evidence suggests that protein kinases are druggable targets for patients with CLL. The emergence of novel and bio-available kinase inhibitors and their promising clinical activity in CLL underscore the oncogenic role of kinases in leukemogenesis. Further investigations directed towards their role as single agents or in combinations may provide insight into understanding the substantial role of kinase-mediated signal transduction pathways and their inhibition in B-CLL.
AB - Introduction : Although protein kinases are primary targets for inhibition in hematological malignancies, until recently their contribution to chronic lymphocytic leukemia (CLL) was poorly understood. Insights into B-cell receptor signaling and its role in regulating key cellular functions have shed light on candidate protein kinases that are aberrantly activated in CLL. In this regard, protein kinases are now considered as potential drug targets in CLL. Area covered : This review has covered signaling pathways and associated protein kinases in CLL and the kinase inhibitors currently available in preclinical and clinical investigations. Individual protein kinases that are abnormally active in CLL and the functional consequences of their inhibition are discussed. Expert opinion : A growing body of evidence suggests that protein kinases are druggable targets for patients with CLL. The emergence of novel and bio-available kinase inhibitors and their promising clinical activity in CLL underscore the oncogenic role of kinases in leukemogenesis. Further investigations directed towards their role as single agents or in combinations may provide insight into understanding the substantial role of kinase-mediated signal transduction pathways and their inhibition in B-CLL.
KW - B-cell receptor
KW - Chronic lymphocytic leukemia
KW - Protein tyrosine kinase
KW - Receptor tyrosine kinase
KW - Tyrosine kinase inhibitor
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U2 - 10.1517/13543784.2012.668526
DO - 10.1517/13543784.2012.668526
M3 - Review article
C2 - 22409342
AN - SCOPUS:84858162638
SN - 1354-3784
VL - 21
SP - 409
EP - 423
JO - Expert Opinion on Investigational Drugs
JF - Expert Opinion on Investigational Drugs
IS - 4
ER -