Summary: giant cell tumor of bone Safety and efficacy of denosumab for giant cell tumor of bone – What have we learnt, and where to from here?

Summary: chondrosarcomas GDC-0449 in patients with advanced chondrosarcomas: a French/US and French National Cancer Institutes Phase II collaborative study (Italiano) Outcomes of inoperable central chondrosarcoma (Picci) SRC signaling is involved in chemoresistance and migration of chondrosarcoma cells (van Oosterwijk)

POSTER: MTORC1 inhibitor targets SRC oncogenic signaling via MIRs in human chondrosarcoma PRP1 (an MTORC1 inhibitor) targets SRC via upregulation of MIR181A/99A/450A/199b5b SRC downregulates these MIRs MIR99A regulates MTOR/FGFR3 Complex feedback loops involving RAS/MAPK and PI3K pathways PRP1 has cytostatic effects Galoian, Temple

Summary: chordoma High-dose single fraction radiotherapy for the management of chordomas of the spine and sacrum (Yamada et al) Germline polymorphisms in brachyury chordoma risk (Flanagan et al) The landscape of mutations in chordoma: PIK3CA and epigenetic modifiers (Campbell)

POSTER: HDAC inhibitor (Panobinostat) effects on mesenchymal tumors and chordomas Panobinostat inhibits growth of chondrosarcoma line JJ012 No effect on chordoma lines Effects independent on effects on ubiquitin ligase pathway Suggest combinations with other agents where resistance exists Galoian, Temple

HIF-1 Signaling in Chordoma is Identical to Nucleus Pulposus and Confers Survival Advantage in Hypoxic Environment John A Abraham, MD 1 Francis J Hornicek MD PhD 2 Irving Shapiro PhD 1 Makarand Risbud PhD 1 1 Rothman Institute at Thomas Jefferson University Philadelphia, PA 2 Massachussetts General Hospital Boston, MA

Hypothesis: – Chordoma is embryologically similar to nucleus pulposus cells – HIF-1 is an important factor in protecting NP cells from apoptosis in the hypoxic conditions in which they reside. – The purpose of this study was to determine if a similar mechanism could be functioning in Chordoma cells. Summary of Findings – Chordoma and NP cells show identical patterns of HIF-1  expression under normoxic and hypoxic conditions, unlike cells derived from most other tissues – Transcription of HIF-1 in both Chordoma and NP increases significantly in hypoxic conditions – Hypoxia protects NP cells from apoptotic stimuli. Serum starvation under hypoxic conditions produces significantly less apoptosis that under normoxic conditions Discussion – HIF-1 is likely a key factor in Chordoma cell survival under hypoxic conditions. – Interruption of HIF-1 signaling may be a therapeutic mechanism HIF-1 Signaling in Chordoma is Identical to Nucleus Pulposus and Confers Survival Advantage in Hypoxic Environment