Steven W. Elmore

TL;DR: Mechanistic studies reveal that ABT-737 does not directly initiate the apoptotic process, but enhances the effects of death signals, displaying synergistic cytotoxicity with chemotherapeutics and radiation.

TL;DR: The re-engineering of navitoclax is reported to create a highly potent, orally bioavailable and BCL-2–selective inhibitor, ABT-199, which inhibits the growth of BCL–dependent tumors in vivo and spares human platelets, indicating that selective pharmacological inhibition of Bcl-2 shows promise for the treatment of B CL-2-dependent hematological cancers.

TL;DR: The biological properties and rationale for clinical trials evaluating ABT-263 in small-cell lung cancer and B-cell malignancies are provided and the oral efficacy should provide dosing flexibility to maximize clinical utility both as a single agent and in combination regimens are reported.

TL;DR: Navitoclax showed a pharmacodynamic effect on circulating platelets and T cells and has a novel mechanism of peripheral thrombocytopenia and T-cell lymphopenia, attributable to high-affinity inhibition of Bcl-XL and BCL-2, respectively.

TL;DR: BCL-XL–selective inhibitors have the potential to enhance the efficacy of docetaxel in solid tumors and avoid the exacerbation of neutropenia observed with navitoclax, and demonstrate the translational utility of this toolkit of selective BCL-2 family inhibitors.