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Abramson Cancer Center Director’s Leadership Council March 13, 2017 “Bringing the Noise: Changing the Face of the Silent Killer” Gynecologic Oncology Program Ronny Drapkin, MD, PhD Director, Penn Ovarian Cancer Research Center Director, Gynecologic Oncology Research, Basser Center for BRCA Robert Burger, MD Director, Clinical Research Mark Morgan, MD Chief, Gynecologic Oncology • There are 240,000 new cases of ovarian cancer diagnosed each year – 152,000 deaths/yr • 70-80 % of women are diagnosed with late stage disease • Lack of screening tool for early detection • Limited understanding of molecular pathogenesis • Most lethal gynecologic malignancy % 5-year survival Ovarian Cancer – The ‘Silent’ Killer 90 80 70 60 50 40 30 20 10 0 1 2 3 4 Clinical Stage Tumor Why Penn? • • • • Unique commitment to Gynecologic Cancers Penn Ovarian Cancer Research Center - 2007 Basser Center for BRCA – 2012 Collaborators across other Philadelphia-based institutes • Collaborative environment “In the long history of humankind (and animal kind, too) those who learned to collaborate and improvise most effectively have prevailed.” Charles Darwin On the Origin of Species, 1859 Goals of Ovarian Cancer Research Center (OCRC) • Develop a comprehensive understanding of ovarian cancer pathogenesis. • Develop new methods for early detection and prevention of ovarian cancer. • Characterize the genetic factors that drive the development of hereditary (BRCA) and sporadic forms of ovarian cancer. • Develop new approaches to treat and prevent ovarian cancer. • Support clinical trials to assess safety and efficacy of new treatments. BRCA as a Model for Early Ovarian Cancer Opportunity to evaluate the tubes and ovaries in women who undergo prophylactic salpingo-oophorectomy and detect tumors early in their course “Ovarian Cancers” actually start in the Fallopian Tube, not the Ovary! Impact of Fallopian Tube • Prevention: – Remove tissue at risk complications: • “Surgical menopause” – SGO recommendation for women at risk: • Two-step risk reduction – Recommendation for women at average risk: • Opportunistic salpingectomy at time of hysterectomy, in lieu of tubal ligation, other pelvic surgery • Early Detection: – CA125: inadequate for early detection – Transvaginal Ultrasound: inadequate for early detection – New BINARY biomarkers for ovarian cancer Perets and Drapkin, Cancer Res, 2016 Gyn Oncology Immunotherapy • CAR T-Cell Therapy Trials: – Mesothelin – Folate Receptor • Vaccine Trials: – Mesothelin – Survivin • Chemo + Checkpoint inhibitors: – Ab against PD-L1 (Avelumab) – Ab-drug conjugate against Folate Receptor – Dual checkpoint inhibitors Janos Tanyi, Dan Powell, Robert Burger Penn Ovarian Cancer Research Center PDX Platform • Primary Orthotopic PDX model with patient-matched immunity – PI: F. Simpkins lab • Metastatic Orthotopic PDX models – PI: R. Drapkin lab George et al., JCI Insight, 2017 Liu et al., CCR, 2017 Volume of GYN Biospecimens Tumor type HUP PAH CCH Penn MedVirtua Ovarian 80 35 20 emerging Endometrial 100 100 90 emerging Cervix 40 25 10 emerging Other 40 30 10 emerging LONGitudinal Genomic PROFILing (LONG PROFILE) PDX-Assisted THerapeutics FOR Women At Recurrent Disease (PATH FORWARD) BIOmarkers for Ovarian Cancer (BioOvCa) Diagnosis OCRC Tumor Bank Treatment Recurrence Rationale Evidence-Based MAINtenance (REMAIN) Rapid Autopsy Program (RAP) Death CAR T-Cell Therapy ? ncRNAs ? Clinical Trials