Plasma Membrane and Actin Cytoskeleton as Synergistic Barriers to Nanowire Cell Penetration
2014; 30 (41): 12362-12367
Bruton's tyrosine kinase inhibitors and their clinical potential in the treatment of B-cell malignancies: focus on ibrutinib.
Therapeutic advances in hematology
2014; 5 (4): 121-133
Quantification of nanowire penetration into living cells.
2014; 5: 3613-?
Aberrant signaling of the B-cell receptor pathway has been linked to the development and maintenance of B-cell malignancies. Bruton's tyrosine kinase (BTK), a protein early in this pathway, has emerged as a new therapeutic target in a variety of such malignancies. Ibrutinib, the most clinically advanced small molecule inhibitor of BTK, has demonstrated impressive tolerability and activity in a range of B-cell lymphomas which led to its recent approval for relapsed mantle cell lymphoma and chronic lymphocytic leukemia. This review focuses on the preclinical and clinical development of ibrutinib and discusses its therapeutic potential.
View details for DOI 10.1177/2040620714539906
View details for PubMedID 25360238
Bruton tyrosine kinase inhibitors: a promising novel targeted treatment for B cell lymphomas
BRITISH JOURNAL OF HAEMATOLOGY
2013; 163 (4): 436-443
High-aspect ratio nanostructures such as nanowires and nanotubes are a powerful new tool for accessing the cell interior for delivery and sensing. Controlling and optimizing cellular access is a critical challenge for this new technology, yet even the most basic aspect of this process, whether these structures directly penetrate the cell membrane, is still unknown. Here we report the first quantification of hollow nanowires-nanostraws-that directly penetrate the membrane by observing dynamic ion delivery from each 100-nm diameter nanostraw. We discover that penetration is a rare event: 7.1±2.7% of the nanostraws penetrate the cell to provide cytosolic access for an extended period for an average of 10.7±5.8 penetrations per cell. Using time-resolved delivery, the kinetics of the first penetration event are shown to be adhesion dependent and coincident with recruitment of focal adhesion-associated proteins. These measurements provide a quantitative basis for understanding nanowire-cell interactions, and a means for rapidly assessing membrane penetration.
View details for DOI 10.1038/ncomms4613
View details for PubMedID 24710350
Constitutive or aberrant signalling of the B cell receptor signalling cascade has been implicated in the propagation and maintenance of a variety of B cell malignancies. Small molecule inhibitors of Bruton tyrosine kinase (BTK), a protein early in this cascade and specifically expressed in B cells, have emerged as a new class of targeted agents. There are several BTK inhibitors, including ONO-WG-307, LFM-A13, dasatinib, CC-292, and PCI-32765 (ibrutinib), in preclinical and/or clinical development of which ibrutinib is currently in phase III trials. Recent clinical data suggest significant activity of ibrutinib as a first in class oral inhibitor of BTK. This review provides an overview of ongoing clinical studies of BTK inhibitors.
View details for DOI 10.1111/bjh.12573
View details for Web of Science ID 000326034200004
View details for PubMedID 24111579