1. 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 1

2. Ovarian Cancer – The ‘Silent’ Killer10 20 30 40 50 60 70 80 90
% 5-year survival 1 2 3 4
Clinical Stage
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
Tumor
Basic overview of clinical scenario

3. Why Penn? Unique commitment to Gynecologic Cancers
Penn Ovarian Cancer Research Center
Basser Center for BRCA – 2012
Collaborators across other Philadelphia-based institutes
Collaborative environment
Why study ovarian cancer at Penn.
Why did I come here from Harvard.
“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

4. 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.
The ultimate goal of these programs is to improve the quality of life for women with ovarian cancer and provide guidance and support to their families.

5. 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
But the prophylactic removal of the tubes and ovaries in women with BRCA mutations afforded pathologists an opportunity to carefully examine these tissues for occult cancer, cancers that were not clinically evident.
And in a series of studies that span about 6 years while I was at the Dana-Farber Cancer Institute in Boston, we found that most SEROUS ovarian cancers actually arise from the fallopian tube epithelial cells, not the ovary.
This observation has now been reproduced in centers around the world and it has become generally accepted that the fallopian tube is the site of origin.
This paradigm shift has had tremendous impact on our approaches to early detection (we’ve been looking in the wrong place for a long time), prevention (can we consider just removing the fallopian tubes and spare women the surgical menopause that they are put into with the combined surgery? An area of active debate), and defining new therapeutic targets.
“Ovarian Cancers” actually start in the Fallopian Tube, not the Ovary!

6. 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

7. Perets and Drapkin, Cancer Res, 2016

8. Gyn Oncology Immunotherapy
CAR T-Cell Therapy Trials:
Mesothelin
Folate Receptor
Vaccine Trials:
Survivin
Chemo + Checkpoint inhibitors:
Ab against PD-L1 (Avelumab)
Ab-drug conjugate against Folate Receptor
Dual checkpoint inhibitors
Janos Tanyi, Dan Powell, Robert Burger

9. 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

10. Volume of GYN Biospecimens
Tumor type
HUP
PAH
CCH
Penn Med-Virtua
Ovarian 80 35 20
emerging
Endometrial
100 90
Cervix 40 25 10
Other 30
Penn Medicine Virtua in Lumberton, NJ

11. Rationale Evidence-Based MAINtenance (REMAIN) BIOmarkers for
Diagnosis
Treatment
Recurrence
Death
Rapid Autopsy
Program (RAP)
Rationale Evidence-Based
MAINtenance
(REMAIN)
BIOmarkers for
Ovarian Cancer
(BioOvCa)
LONGitudinal Genomic
PROFILing
(LONG PROFILE)
PDX-Assisted
THerapeutics FOR
Women At Recurrent
Disease (PATH FORWARD)
OCRC Tumor Bank

12. ? BRCA New Models Clinical Trials ncRNAs Pathogenesis Biomarkers
CAR T-Cell
Therapy
Tumor
Immunology
Blood
Vessels
Vaccines ?
ncRNAs
Pathogenesis
BRCA
New Models
Clinical
Trials

13. ….we have to build bridges.

14. This is a photo of a corn silo in Iowa that I took during a recent visit.
Silos are great for storing food and when it comes to science, that is about it.
Silos have no place in the modern biomedical research area. We can’t work alone.
No one has the resources to address the vexing problems of cancer biology alone and even if you did you couldn’t possible attack the problem from multiple angles.
Instead…..