February 3-5, 2016 | Lansdowne Resort, Leesburg, VA

Shaping the Future of Cancer Prevention

The Changing Landscape

Scott M. Lippman, MD

Director, UC San Diego Moores Cancer Center

“If we can intercept cancer very early, if we can even prevent it, that’s the way that I

think we can really start talking about the ways to cure cancer.”

~ Elizabeth Blackburn – Davos Annual Meeting 1/20/2016

• Prevention and Cancer Vaccine Development

• Early Cancer Detection

• Cancer Immunotherapy and Combination Therapy

• Genomic Analysis of Tumor and Surrounding Cells

• Enhanced Data Sharing

Jun 2011

Feb. 1 Release

The White House Fact Sheet

Thomas W. Kensler, Avrum Spira, Judy E. Garber, Eva Szabo, J. Jack Lee, Zigang Dong, Andrew J. Dannenberg, William N. Hait,

Elizabeth Blackburn, Nancy E. Davidson, Margaret Foti, and Scott M. Lippman

January 7, 2016

Bad Luck?

Jan 2015

Dec 2015

Epithelial Cancer

(tumor / pre-cancer pairs)• Shain AH, et al. N Engl J Med 2015 (Nov)

(melanoma / precursor; n=37; WES)

• Stachler MD, et al. Nat Gen 2015 (Sep)

(esophagus / BE; n=25; WES)

• Ross-Innes CS, et al. Nat Gen 2015 (Sep)

(esophagus / BE; n=23; WGS)

• Sakr RA, et al. Mol Oncol 2015 (Nov)

(ILC / LCIS; n=19; WES)

- Driver mutations detected in plasma

Izumchenko E, et al., Nat Commun 2015 (Sep)(ctDNA in AAH; n=2)

New Blood Cancer Premalignant State

- clonal hematopoiesis• 2014 (December)

Jaiswal S, et al. N Engl J Med

Genovese G, et al. N Engl J Med

• 2015 (5 papers: Blood, Nature, NEJM)

+

+ Kaufman, Science 2016 (epigenetic reprogramming)

Kato*, Lippman*, Flaherty, Kurzrock. JNCI 2016 (in press)

clonally relatedclonally unrelated

Biology of Premalignancy: Genomics

WES

Spira A, et al.

Nature Med 2007

Whitney DH, et al.

BMC Med Genomics 2015

First validated genomic markers • Imperiale TF, et al. N Engl J Med 2014

• Silvestri GA, et al. N Engl J Med 2015

Early Detection: Genomics

Novel approaches; Big Data• Barrett C, et al. PNAS 2015

RNA

Concept: Pap smears for early

detection of ovarian cancer

(ovarian cancer)

Liquid Biopsy• Sausen M, et al. Nat Commun 2015

Cell-free plasma DNA

Illumina

The Case for a Pre-Cancer Genome Atlas (PCGA)

Genome-wide Sequencing (ng DNA/RNA, single cell)

Computational Biology

Inflammatory TME

Campbell JD, et al.

CAPR 2016 (in press)

Immune

Cells

Liquid Biopsy Technologies

Roadmap for Multi-center PCGA Effort

Inflammatory, Immunosuppressive TME

Chu NJ, et al. Clin Cancer Res 2015

Mice < 2 mos (early PanIN) Mice > 2 mos (late PanIN)

Keenan BP, et al.

Gastroenterology 2014 Listeria Vaccine (LM-Kras) and Depletion of Treg CellsOther Immunoprevention• Vaccines to MUC1 (O. Finn) and HER2 (M. Disis)

• Vaccines for BRCA1 carriers / Lynch syndrome

• Immune effects of metformin (PLoS One 2015) and

tamoxifen (Nat Commun 2015)

Early stage PanIN1 Mid stage PanIN2 PDA

Kras-p53-Cre pancreatic mouse model

Inflammatory TME: Microbiome

COLORECTAL

Grivennikov SI…Karin M. Nature 2012

Iida N, et al. Science 2013

Viaud S, et al. Science 2013

Levy J, et al. Nature Cell Biol 2015

Garrett WS. Science 2015 Forslund K, et al. Science 2015

- Dietary Obesity Alters Microbiota,

Promoting HCCYoshimoto S, et al. Nature 2013

Chemoprevention: New Standards / Milestones 2015

Sep 2015

– First USPSTF recommendation since 2002 (tamoxifen)

– Prognostic/predictive biomarkers within prostaglandin pathway

(Cancer Prev Res 2014; Sci Transl Med 2014; JAMA 2015)

Mar 2015

– First FDA registration trial in this setting 2016

October 22, 2015

– Targeting DNA repair in skin cancer

– Consistent with earlier RCT

(xeroderma pigmentosum; Lancet 2001)

November 5, 2015

Duodenal Polyp Burden

Samadder NJ, et al. DDW Presidential Plenary 2015

Breakthrough Combination: Targeting

Wnt and EGFR pathways in FAP

Implementation Science

- Tobacco, obesity, physical activity

- Screening: CRC, breast, lung

Lynch Syndrome

• CRC tumor testing for MMR, MSI

(Hampel H, et al. JNCCN 2010; Hampel H, et al. JCO 2008; Hampel H, et al. NEJM 2005)

• To identify LS families (for intensive surveillance) and MSI+ patients (e.g., anti-PD-1; Le, et al. NEJM 2015)

• Recommended by EGAPP, NCCN, USMTF on CRC, ACG, and SGO/ACOG

• Data supporting endometrial cancer in GOG/NRG (Goodfellow PJ, et al. J Clin Oncol 2015 Dec)

Mar 2012

HPV Vaccines

Boys and girls age 11-12, three (3) doses (CDC, ACIP)

Utilization: 36% girls, 14% boys (3 doses); even lower in Hispanics, Blacks,

poor; healthcare disparity even greater globally (> 600,000 cancer cases/year)

Barriers

• Limited understanding

• Missed additional doses

• Cost / safety concerns

Roadmap to increased vaccination uptake

• Shift focus from behavior associated with

infection to preventing major cancers

• Further study of 1 vs. 3 doses

American Academy of Family Physicians

American Academy of Pediatrics

American College of Obstetricians and Gynecologists

American College of Physicians

Centers for Disease Control and Prevention

Immunization Action Coalition

American Cancer Society

American College of Obstetrics and Gynecology

American Dental Association

American Head and Neck Society

American Nurses Association

American Pharmacists Association

Association of Immunization Managers

Society for Adolescent Medicine

Society of Gynecologic Oncology

February 3-5, 2016 | Lansdowne Resort, Leesburg, VA

The Changing Landscape of

Cancer Prevention

February 3-5, 2016 | Lansdowne Resort, Leesburg, VA

Program

Day 1 (sessions 1-6)

• Biology of premalignancy / prevention

• Germline mutations and cancer predisposition genes

• Lifestyle, environmental risk factors

• Energetics, chronic inflammation, microbiome

• Health disparities and Implementation science

Day 2 (sessions 7-14)

• Chemoprevention X 2 (including precision approaches)

• Early detection X 2 (including genomic approaches)

• HPV; non-viral (cancer) vaccines

• Survivorship

• Quantitative sciences

Day 3: Summary reports; Prioritization, next steps

February 3-5, 2016 | Lansdowne Resort, Leesburg, VA

Goals and Objectives

• Review state of the science, challenges, and opportunities

• Identify priorities, future directions for cancer prevention, including

early detection

• Determine the best way to organize AACR’s support of the cancer

prevention scientific community through communications,

meetings, journals, education

• Discuss how AACR can best serve the public by advancing public

policy, public education, and services in cancer prevention

• Identify how best to collaborate with relevant sectors to advance

cancer prevention on a national and international level