Bäuerle et al. Page 3215

Angiogenesis plays a crucial role in the development of bone metastases. To examine vascular changes in experimental breast cancer bone metastases upon treatment with zoledronic acid and sunitinib malate, Bäuerle and colleagues used dynamic contrast enhanced MRI and vessel size imaging in a longitudinal in vivo study. Resulting parameters from noninvasive imaging indicated vessel remodeling in these osseous lesions after application of zoledronic acid and sunitinib malate, which could be assessed before antiresorptive and antitumor effects of these treatments were detected. These results suggest that imaging could be used for early assessment of treatment response in malignant bone lesions.

Bates Page 3105

In recent years, the study of cancer stem cells (CSCs) has garnered much attention. In this issue of CCR Focus, guest editor Percy Ivy provides an overview of research surrounding CSCs and addresses some of the controversies in the field. Topics in CSC biology are discussed, including CSC identification and characterization, the CSC self-renewal pathway, and interaction of CSCs with the microenvironment. A particular emphasis is placed on translating our underlying knowledge of CSC biology into the development of anticancer therapeutics, and efforts to target several pathways involved in CSCs, including the Wnt, Notch, and Hedgehog signaling pathways, are described.

Milde et al. Page 3240

Histone deacetylases (HDACs) 1–11 are differentially expressed in cancer tissues; however, more research is needed on the role of individual HDACs in tumor biology. In this study, Milde and colleagues found that class II HDACs 5 and 9 were significantly upregulated in medulloblastoma tumors with poor prognosis, and high HDAC5 and HDAC9 mRNA expression was an independent risk factor for poor survival in multifactorial analysis. Furthermore, siRNA-mediated knockdown of HDAC5 or HDAC9 resulted in decreased tumor cell growth. These findings implicate HDAC5 and HDAC9 as potential therapeutic targets in medulloblastoma.

Malmström et al. Page 3279

Local CD40-directed therapies, which aim to tilt tumor-induced immunosuppression in favor of antitumor responses, have shown promise in experimental models. Malmström and colleagues used adenovector-based gene therapy to introduce the human CD40 ligand (CD40L) gene into the tumor milieu. In a Phase I/IIa trial of patients with urinary bladder carcinoma, they found that AdCD40L therapy was safe and that it stimulated a massive immune cell infiltration into the bladder wall. Further, several patients had few, or no, remaining high-grade malignant cells following treatment. These results suggest that AdCD40L therapy has potential for local application on patients with solid tumors.