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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.

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summary giant cell tumor of bone
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
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
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
Summary: chordoma
  • High-dose single fraction radiotherapy for the management of chordomas of the spine and sacrum (Yamada et al)
  • Germline polymorphisms in brachyurychordoma 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
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

slide9

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

MakarandRisbud PhD 1

1Rothman Institute at

Thomas Jefferson University

Philadelphia, PA

2Massachussetts General Hospital

Boston, MA

slide10

HIF-1 Signaling in Chordoma is Identical to

Nucleus Pulposus and Confers

Survival Advantage in Hypoxic Environment

  • 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-1a 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