Highlights of This Issue

Abstract

Kinesin spindle protein (KSP) is a mitotic kinesin, and inhibition of this motor protein results in mitotic arrest and cell death. Basso and colleagues identified SCH 2047069, a novel KSP inhibitor with oral bioavailability and the ability to cross the blood brain barrier. The ability to dose the compound orally provides convenience of dosing as well as the ability to achieve more continuous exposure via the use of dose-dense administration. SCH 2047069 demonstrates potent pharmacodymanic marker activity in vitro and in vivo and antitumor activity in a variety of preclinical models as a single agent and in combination with paclitaxel, gemcitabine, or vincristine.ABT-263 is a first-in-class BCL2 family inhibitor that restores the ability of cancer cells to undergo apoptosis. However, many cancer cells are resistant to ABT-263 due to high expression of a BCL2 family member MCL1. MicroRNAs are small noncoding RNAs that have been shown to abnormally regulate in cancer cells. Lam and colleagues screened a library of 810 human microRNAmimics to explore its role in ABT-263 sensitivity. They identified microRNAs that restore apoptosis in the presence of ABT-263 by reducing MCL1 protein expression. Their data can facilitate the design of microRNA replacement therapies to increase sensitivity to BCL2 antagonists.Microtubule-associated protein Tau has been reported to be a predictive factor for clinical response to taxanes in metastatic breast cancer. Spicakova and colleagues studied the expression and function of Tau in several breast cancer cell lines. They derived three independent T-47D clones stably overexpressing Tau-3R and Tau-4R isoforms, and showed no change in taxane sensitivity compared to parental cells transfected with vector alone. Knock down or silencing of Tau expression in three cell lines that expressed Tau constitutively did not result in increased taxane sensitivity. Thus, neither overexpression nor depletion of Tau modulate cellular sensitivity to taxanes. Tau overexpression is not a mechanism of taxane resistance in breast cancer.