PL1.2. Tumour-bone cell interactions in malignancy

Cancer Treatment Reviews (2008) 34, S43– S86

available at www.sciencedirect.com

journal homepage: www.elsevierhealth.com/journals/ctrv

Abstracts: VII International meeting on cancer induced bone disease Plenary Lectures PL1 Plenary Session PL1.1. Preparing the soil – the bone marrow niche G. Mundy Nashville, USA Abstract not received. doi:10.1016/j.ctrv.2008.03.126

PL1.2. Tumour-bone cell interactions in malignancy T. Guise Charlottesville, USA Abstract not received. doi:10.1016/j.ctrv.2008.03.127

PL1.3. Developments in bone target treatment of cancer G. David Roodman

onate. Further, preclinical studies show that RANKL decreased bone metastasis and tumor growth in mice. Similarly, studies with a TGF-b receptor-1 kinase inhibitor demonstrated it decreased both development of lung and bone metastasis, tumor growth and expression of av b3, which is involved in tumor cells homing to bone and osteoclastic bone destruction. Recently, endothelin-1 has been identified as an osteoblast stimulating factor produced by breast and prostate cancer cells. In preclinical models, blocking the endothelin-1A receptor decreased tumor growth and development of osteoblastic metastasis. Clinical trials with atrasentan, which targets the endothelin-1 receptor-A, showed a significant decrease in cancer-induced bone pain and bone specific alkaline phosphatase and improved quality of life for patients. Further, prostate cancer patients with only bone metastasis had delayed disease progression, suggesting that targeting the bone microenvironment can have profound effects in prostate cancer. Most recently, studies of myeloma patients treated with the proteasome antagonist, bortezomib, have shown increases in serum bone formation markers and increased osteoblastic activity in bone biopsies from myeloma patients who respond to bortezomib. Bone formation is usually suppressed in myeloma patients. Thus, promising new therapies are under development for this devastating complication of malignancy. doi:10.1016/j.ctrv.2008.03.014

Pittsburgh, USA

PL2 The metastatic problem Identification of the pathophysiologic mechanisms responsible for the bone destruction and new bone formation associated with cancer bone metastasis has provided important new therapeutic targets for treating bone metastasis. Among these novel targets are RANKL, which induces osteoclast formation and is a chemotactic factor for cancer cells, TGF-b, which stimulates expression of avb3 cancer cells and PTHrP production, PTHrP in epithelial tumors and endothelin-1 in osteoblastic bone metastasis. Treatment with a monoclonal anti-RANKL antibody, denosumab, significantly decreased bone resorption markers for up to 90 days after a single injection and is equally efficacious as pamidr-

doi:10.1016/j.ctrv.2008.03.004

PL2.1. M for invasion: Morphology, mutation and the microenvironment A. Anderson Dundee, UK Cancer is a complex, multiscale process, in which genetic mutations occurring at a subcellular level manifest themselves as functional changes at the cellular and tissue scale. The importance of tumour cell/microenvironment