Resistance to chemotherapy is a major hurdle for treating cancer patients. Combining NEK2 inhibitors with taxanes may be viable approach for improving patient outcomes by enhancing mitotic defects induced by taxanes alone.

Polysaccharide deacetylases are bacterial enzymes that catalyze the deacetylation of acetylated sugars on the membranes of Gram-positive bacteria, allowing them to be unrecognized by host immune systems. Inhibition of these enzymes would disrupt such pathogenic defensive mechanisms and therefore offers a promising route for the development of novel antibiotic therapeutics. Here, the first X-ray crystal structure of BA0150, a putative polysaccharide deacetylase from Bacillus anthracis, is reported to 2.0 Å resolution. The overall structure maintains the conserved (α/β)8 fold that is characteristic of this family of enzymes. The lack of a catalytic metal ion and a distinctive metal-binding site, however, suggest that this enzyme is not a functional polysaccharide deacetylase.

Chromosomal instability (CIN), or the dynamic change in chromosome number and composition, has been observed in cancer for decades. Recently, this phenomenon has been implicated as facilitating the acquisition of cancer hallmarks and enabling the formation of aggressive disease. Hence, CIN has the potential to serve as a therapeutic target for a wide range of cancers. CIN in cancer often occurs as a result of disrupting key regulators of mitotic fidelity and faithful chromosome segregation. As a consequence of their essential roles in mitosis, dysfunctional centrosomes can induce and maintain CIN. Centrosome defects are common in breast cancer, a heterogeneous disease characterized by high CIN. These defects include amplification, structural defects, and loss of primary cilium nucleation. Recent studies have begun to illuminate the ability of centrosome aberrations to instigate genomic flux in breast cancer cells and the tumor evolution associated with aggressive disease and poor patient outcomes. Here, we review the role of CIN in breast cancer, the processes by which centrosome defects contribute to CIN in this disease, and the emerging therapeutic approaches that are being developed to capitalize upon such aberrations.