Future directions of bone-targeted therapy for metastatic breast cancer.

Bone is the most common metastatic site for breast cancer, and bone metastases can cause pain as well as risk of pathological fractures. Emerging treatments for metastatic bone disease have arisen from advances in our understanding of the unique cellular and molecular mechanisms that contribute to bone metastasis. The interaction between tumor cells and the bone microenvironment results in a 'vicious cycle' that increases both bone destruction and tumor burden. The tumor secretes factors, such as parathyroid hormone-related peptide, that stimulate osteoclastogenesis. Similarly, the bone stroma produces growth factors, such as transforming growth factor ß, that promote tumor growth in bone. Therapeutic targeting of these microenvironmental factors is under intensive investigation. Other attractive therapeutic targets include signaling molecules, such as receptor activator of nuclear factor κB ligand, Src kinase, and cathepsin K, all of which regulate osteoclast function, and chemokine receptor 4, which is involved in the homing of tumor cells to bone. In this Review, we describe the progress and future directions of novel bone-targeted therapies that may reduce or prevent destructive bone metastasis from breast cancer. Novel modalities for predicting and monitoring treatment response will also be described.

Cell-based and cytokine-directed chemical screen to identify potential anti-multiple myeloma agents.

We used a novel high-throughput drug screening assay, based on Luminex technology, to identify anti-myeloma agents capable of inhibiting cytokines and growth factors essential for multiple myeloma (MM) from a chemical library of 1120 compounds provided by MMRF. Tetracycline derivatives inhibited MM cell proliferation and osteoclast activating factors without obvious effect on cell viability. Steroid compounds specifically decreased angiogenesis-related factors, but stimulated osteoclast activating factors. Antihelmintic drugs potently inhibited cytokines and were cytotoxic. The screen identified potential candidates with potent anti-MM properties that need further investigation.