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Applying Current Findings to Improve the Care of Patients with Ewing Sarcoma

Applying Current Findings to Improve the Care of Patients with Ewing Sarcoma. Steven DuBois, MD Associate Professor of Pediatrics UCSF School of Medicine. EWS/FLI & Olaparib. Garnett et al, 2012. Lessons in Planning PARP Trials. From this morning ’ s talk: Not all inhibitors the same

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Applying Current Findings to Improve the Care of Patients with Ewing Sarcoma

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  1. Applying Current Findings to Improve the Care of Patients with Ewing Sarcoma Steven DuBois, MD Associate Professor of Pediatrics UCSF School of Medicine

  2. EWS/FLI & Olaparib Garnett et al, 2012

  3. Lessons in Planning PARP Trials • From this morning’s talk: • Not all inhibitors the same • Other agents synergize • Relation to DNA damage Garnett et al, 2012 Brenner et al, 2012

  4. Selected Clinical Trials of PARP Inhibitors in Ewing Sarcoma • Adult phase 2 trial of olaparib • 0 / 12 patients with a response (AACR 2013) • Adult phase 1 trial of olaparib + temozolomide • Ongoing • COG phase 1 / 2 trial of BMN-673 + temozolomide • In development • SARC phase 1 / 2 trial of niraparib + temozolomide • In development

  5. Targeting GPR64in Ewing Sarcoma • Orphan receptor • No clinical grade small molecule inhibitors • No clinical grade monoclonal antibodies • Therefore focus on targeting downstream effectors

  6. Targeting MMP-1 in Ewing Sarcoma Yabe et al, 2002 Fuchs et al, 2003

  7. Coussens et al, 2002

  8. Targeting Placental Growth Factor in Ewing Sarcoma Dalal et al, 2005 Bagley et al, 2011

  9. Cautionary Tale of Bevacizumab in Ewing Sarcoma? Boige et al, 2012

  10. Targeting HOXD13 in Ewing Sarcoma • Challenging pharmacologically since a transcription factor (like EWS fusion proteins themselves)

  11. Applying EZH2 and BMI-1 in EWS Richter et al, 2009 Cooper et al, 2011

  12. Bone Marrow Metastatic Disease Oberlin et al, 2006

  13. Acknowledgements NIH/NCI K23 CA154530 Sarcoma Foundation of America Campini Foundation Hope Street Kids Foundation

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