Steven DuBois, MD Associate Professor of Pediatrics UCSF School of Medicine.

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Presentation transcript:

Steven DuBois, MD Associate Professor of Pediatrics UCSF School of Medicine

EWS/FLI & Olaparib Garnett et al, 2012

Brenner et al, 2012 From this morning’s talk: Not all inhibitors the same Other agents synergize Relation to DNA damage

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 temozolomide In development SARC phase 1 / 2 trial of niraparib + temozolomide In development

Orphan receptor No clinical grade small molecule inhibitors No clinical grade monoclonal antibodies Therefore focus on targeting downstream effectors

Yabe et al, 2002 Fuchs et al, 2003

Coussens et al, 2002

Dalal et al, 2005 Bagley et al, 2011

Boige et al, 2012

Challenging pharmacologically since a transcription factor (like EWS fusion proteins themselves)

Richter et al, 2009 Cooper et al, 2011

Oberlin et al, 2006 StudyPatients with Any Marrow Involvement Patients with Isolated Marrow Involvement Ladenstein et al, / 271 = 45%19 / 271 = 7% Bernstein et al, 2006 Not Reported8 / 110 = 7% Oberlin et al, / 97 = 24%3 / 97 = 3%

NIH/NCI K23 CA Sarcoma Foundation of America Campini Foundation Hope Street Kids Foundation