Cancer Research at UNC: Lineberger CCC Update Why I took this job: I was offered job running oncologic drug discovery at large pharma. While considering that option, I realized I was passionate about basic cancer research and its clinical translation. Given my love for UNC, I could not imagine better place to be Cancer Center Director Lisa A. Carey, MD Jacobs Preyer Distinguished Professor for Breast Cancer Research Associate Director, Clinical Sciences Lineberger Comprehensive Cancer Center

UNC Lineberger: NC’S PUBLIC COMPREHENSIVE CANCER CENTER. AREAS OF FOCUS Basic Research Population Sciences Research Clinical and Translational Research Dissemination and outreach in NC Economic Development Clinical Excellence NC’s Matrix Ca Ctr embedded within UNC

UNC Lineberger History “Comprehensive” Designation Marsico Hall University Cancer Research Fund Starts NC Cancer Hospital 1974 1990 1995 2008 2009 2014 NCI Designation; Joe Pagano, PhD First Director H. Shelton Earp III, MD Second Director Norman E Sharpless, MD Third Director

LCCC: Who We Are And How We Do It 2010 2014 LCCC Members 295 300 LCCC space (square feet) 100K 153K NCI Funding $64m $71m All Cancer Funcing $220m $210m Cancer Patients on Trials Testing Interventions 1,079 1,731 Take home is we are vibrant growing cancer center Great growth in accruals, NCI funding, PPGS, space Membership and funding have held steady b/c advice of our EAB, as new director, to enhance cancer focus. Scrutinized grants and membership; and reduced both significantly Members have $280M in funding.

Growth in NCI Funding 2014 NCI FUNDING: Stanford $55M Michigan $54M Wash U $42M Duke $34M UNC $58M (6th among matrix cancer centers) 25 http://report.nih.gov/award/index

One of the Reasons UNC is Great NC Cancer Hospital UNC Lineberger Marsico Hall Dental School School of Nursing Eshelman School of Pharmacy Gillings School of Global Public Health

RESEARCH PROGRAMS

Cancer in North Carolina Cancer Deaths/100K Key AA-White Mortality Disparities Lung (53.2) Prostate (2.8-fold) Prostate (23.4) Endometrial (2.3-fold) Breast (22.4) Myeloma (2.2-fold) Colon (14.8) Head &Neck (2.0-fold) Pancreas (10.5) Cervix (1.9-fold) Colon (1.5-fold) Breast (1.4-fold) Population: 9.9M Annual Cancer Cases: 52,550 Annual Cancer Deaths: 19,300 22% African American, 9% Hispanic

UNC LCCC Disparities Research Prostate – North Carolina-Louisiana Prostate Cancer Project Endometrial – minority obesity interventions/metformin trial Multiple Myeloma –North Carolina Multiple Myeloma Network Head and Neck – Carolina Head and Neck Cancer Study Cervical – HPV vaccine and screening interventions Colorectal – Colonoscopy interventions in African-American and Hispanic populations Breast – Carolina Breast Cancer Study Lung – Intervention to increase early detection and lung cancer surgery in African American populations Bladder – Investigating sub-types in African American populations

Understanding Cancer in NC: ICISS Combines Tumor Registry: 100% - 320,000 cases (2005-2013) With Health Care Claims: Medicare, Medicaid, private payers, State Employees = 80% of NC cancers (~255,000 cases) Involves 4 UNC schools, 16 departments, 4 programs Powerful tool: Understanding how patients are being treated in NC & how well they do STEPHANIE WHEELER (SPH) ETHAN BASCH (Heme/Onc) RON CHEN (Radiation Onc) ANNE-MARIE MEYER (SPH)

Carolina Breast Cancer Study (CBCS) Large population-based study of breast cancer Combined classical and molecular epidemiology. CBCS1 (1993-1996); CBCS2 (1996-2001). CBCS1/2: >100 Publications CBCS3 2008-2013, followup x 10y ANDY OLSHAN (Chair, UNC Epi) Enrollment by Race Identified Black/White disparities in: Type of breast cancer Access and adherence to drugs Survival

Cancer Genetics: National Leadership CHUCK PEROU, KATIE HOADLEY LCCC 1108 –UNCseq Over 1,700 patients consented 28 tumor types 10,000 samples >100 trillion bases NEIL HAYES --Hoadley, Cell, 2014 https://www.youtube.com/watch?v=Y9HumO20GKc

LCCC Sequencing Trials DNA RNA CBCS3 (3,000 germlines) TCGA (10,000 tumors) Integrated Translational Science Center Integrated Translational Science Center (tumor) Retrospective CBCS3 (3,000 tumors) Investigator-initiated studies National Cooperative Group trials Investigator-initiated studies UNCseq (1,700 patients to date, tumor and germline) UNCseq Integrated Translational Science Center Integrated Translational Science Center (tumor) Qiuickly say this is provided as reference Prospective “Window” drug trials in melanoma, breast cancer, lymphoma NCGenes (germline)

Novel Tech: Carbon Nanotube X-rays DEPT. OF PHYSICS AND ASTRONOMY WORKING WITH CLINICAL RADIOLOGY SMALLER, COOLER X-RAY SOURCES CLINICAL APPLICATIONS Chest, breast, dental radiography Hi-energy sources for radiation oncology OTTO ZHOU Just point out here that does radiology and rad onc Comes out of Dept of Physics and Astronomy, now in human clinical trials with CR program (10 minute walk) RAY LEE

Novel Tech: Kinome Profiling Identifying ways that cancer cells RESIST targeted therapy GARY JOHNSON PhD Trials ongoing in melanoma, lung, pancreas, lymphoma and breast cancer LISA CAREY MD STERGIOS MOSCHOS MD

Mouse Avatars: Studying Cancer and Drugs COLLABORATIVE CROSS MOUSE PHASE I UNIT 50+ partners in academia and industry 40+ publications (e.g. Cell, Nature, Cancer Cell, Cancer Disco.) 32 funded grant proposals: $25M 5,000 cages for serial housing Small animal imaging (PET/CT, Optical, MRI, U/S) Pharmacokinetics and Pharmacodynamic Monitoring Sharpless et al., Cell 2013 Genetically engineered mice 80+ publications since 2011

Global Oncology NEW NCI FUNDING: U54, NCI supplement (7), R21 (2) DIRK DITTMER BLOSSOM DAMANIA TATA MEMORIAL, MUMBAI MALAWI / ZAMBIA PARTNERSHIP GROESBECK PARHAM YURI FEDORIW SAO PAULO CANCER CENTER MALAWI CANCER PROGRAM JENNIFER SMITH SATISH GOPAL

Patient-Reported Outcomes Methodological leadership of major initiatives at NCI, FDA, PCORI, industry (including development of NCI’s PRO-CTCAE) BRYCE REEVE ETHAN BASCH NEW DEVELOPMENTAL PRO SHARED FACILITY (“PRO-CORE”) Hired software developer Two psychometricians INVOLVES MULTIPLE INVESTIGATORS ACROSS CLINICAL AND PREVENTION PROGRAMS AT LCCC “Patient-reported outcomes is an area of particular strength at UNC, with 6 faculty recruits since the last review including Dr. Bryce Reeve from the NCI, and Dr. Ethan Basch from MSK, who each lead major national and international initiatives in this area.  PROs are now being widely being used by cancer center investigators across multiple programs in clinical research, clinical care, and in registries, and we have a new developmental PRO shared facility to support these efforts.”

Tobacco Centers of Regulatory Science Awards Impact of Tobacco Exposure on Lung’s Innate Defense System Communication on Tobacco Product Risk and FDA Authority Kurt M. Ribisl, PhD Communicating risk to different communities and with different products. Inform FDA regulation. Robert Tarran, PhD All forms of tobacco exposure There are 14 Tobacco Centers of Regulatory Science funded by NIH. (Both are about $19M each if you want to say that) UNC is the only university with 2 TCORS Centers centers. See https://prevention.nih.gov/tobacco-regulatory-science-program/research-portfolio/centers One is led by Kurt Ribisl in CPC and the other by Robert Tarran in Cell Biology. Both centers focus on cigarettes, e-cigarettes, and little cigars Dr. Tarran’s focuses on testing the impact on lung tissue of these 3 products. Dr. Ribisl’s P50 focuses on communicating with tobacco users in new ways about the risks of these products. Early work suggests that flavored e-cigarettes are particularly toxic. This is important because FDA is considering restricting flavors. (if time) Tarran and Ribisl are in regular communication about their studies and help each other out. (Tarran, a basic scientist, recently asked Ribisl which ecig brands to test and Ribisl had market share data that he shared)

Discovering Cancer Drugs CENTER FOR INTEGRATIVE CHEMICAL BIOLOGY AND DRUG DISCOVERY (CICBDD) Cancer drugs in development Scientific focus for future drugs Expansion in 2016 STEPHEN FRYE CICBDD DIRECTOR

New Immunotherapy Program >$20M Investment Manufacturing Facility: Opening 2016 6 T-cell expansion rooms and viral production New Faculty: Barbara Savoldo and Gianpietro Dotti, national leaders, recruited from Baylor. New facility director from St Jude FIRST TRIAL TO START AT UNC IN 2016!

Entrepreneurship

SUMMARY Cancer research at UNC is huge and successful Centered at LCCC, one of the nation’s oldest and largest cancer centers Excellence in public health research, clinical translation, genetics, drug discovery, “big data” analytics and mouse models. Emerging programs in immunotherapy and novel imaging.

Questions?