Shaping the Future of Cancer Prevention The Changing Landscape Scott M. Lippman, MD Director, UC San Diego Moores Cancer Center February 3-5, 2016 | Lansdowne Resort, Leesburg, VA
Feb. 1 Release The White House Fact Sheet • Prevention and Cancer Vaccine Development • Early Cancer Detection • Cancer Immunotherapy and Combination Therapy • Genomic Analysis of Tumor and Surrounding Cells • Enhanced Data Sharing “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 Jun 2011
January 7, 2016 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
Bad Luck? Jan 2015 Dec 2015
Biology of Premalignancy: Genomics + Epithelial Cancer (tumor / pre-cancer pairs) • Shain AH, et al. N Engl J Med 2015 (Nov) (melanoma / precursor; n=37; WES) + Kaufman, Science 2016 (epigenetic reprogramming) • Stachler MD, et al. Nat Gen 2015 (Sep) Kato*, Lippman*, Flaherty, Kurzrock. JNCI 2016 (in press) (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) clonally unrelated clonally related New Blood Cancer Premalignant State - clonal hematopoiesis WES • 2014 (December) Jaiswal S, et al. N Engl J Med Genovese G, et al. N Engl J Med • 2015 (5 papers: Blood, Nature, NEJM )
Early Detection: Genomics First validated genomic markers Imperiale TF, et al. N Engl J Med 2014 • • Silvestri GA, et al. N Engl J Med 2015 Novel approaches; Big Data Concept: Pap smears for early detection of ovarian cancer • Barrett C, et al. PNAS 2015 Spira A, et al. Cell-free plasma DNA Nature Med 2007 Liquid Biopsy Sausen M, et al. Nat Commun 2015 • Illumina (ovarian cancer) RNA Whitney DH, et al. BMC Med Genomics 2015
The Case for a Pre-Cancer Genome Atlas (PCGA) Genome-wide Sequencing (ng DNA/RNA, single cell) Liquid Biopsy Technologies Computational Biology Inflammatory TME Roadmap for Multi-center PCGA Effort Immune Cells Campbell JD, et al. CAPR 2016 (in press)
Inflammatory, Immunosuppressive TME Early stage PanIN1 Mid stage PanIN2 PDA Kras-p53 -Cre pancreatic mouse model Chu NJ, et al. Clin Cancer Res 2015 Keenan BP, et al. Listeria Vaccine (LM-Kras) and Depletion of Treg Cells Gastroenterology 2014 Other 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) Mice < 2 mos (early PanIN) Mice > 2 mos (late PanIN)
Inflammatory TME: Microbiome - Dietary Obesity Alters Microbiota, Promoting HCC Yoshimoto S, et al. Nature 2013 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
Chemoprevention: New Standards / Milestones 2015 Sep 2015 – First USPSTF recommendation since 2002 (tamoxifen) – Prognostic/predictive biomarkers within prostaglandin pathway Breakthrough Combination: Targeting ( Cancer Prev Res 2014; Sci Transl Med 2014; JAMA 2015) Wnt and EGFR pathways in FAP Mar 2015 – First FDA registration trial in this setting 2016 – Targeting DNA repair in skin cancer October 22, 2015 – Consistent with earlier RCT (xeroderma pigmentosum; Lancet 2001) Duodenal Polyp Burden November 5, 2015 Samadder NJ, et al. DDW Presidential Plenary 2015
Implementation Science Mar 2012 - Tobacco, obesity, physical activity - Screening: CRC, breast, lung HPV Vaccines Lynch Syndrome American Academy of Family Physicians American Academy of Pediatrics • CRC tumor testing for MMR, MSI Boys and girls age 11-12, three (3) doses (CDC, ACIP) American College of Obstetricians and Gynecologists American College of Physicians (Hampel H, et al. JNCCN 2010; Hampel H, et al. JCO 2008; Hampel H, et al. NEJM 2005) Utilization: 36% girls, 14% boys (3 doses); even lower in Hispanics, Blacks, Centers for Disease Control and Prevention • To identify LS families (for intensive surveillance) and MSI + patients (e.g., anti-PD-1; Le, et al. NEJM 2015) poor; healthcare disparity even greater globally (> 600,000 cancer cases/year) Immunization Action Coalition American Cancer Society • Recommended by EGAPP, NCCN, USMTF on CRC, ACG, and SGO/ACOG Barriers American College of Obstetrics and Gynecology • Data supporting endometrial cancer in GOG/NRG (Goodfellow PJ, et al. J Clin Oncol 2015 Dec) American Dental Association • Limited understanding American Head and Neck Society • Missed additional doses American Nurses Association American Pharmacists Association • Cost / safety concerns Association of Immunization Managers Society for Adolescent Medicine Roadmap to increased vaccination uptake Society of Gynecologic Oncology • Shift focus from behavior associated with infection to preventing major cancers • Further study of 1 vs. 3 doses
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 February 3-5, 2016 | Lansdowne Resort, Leesburg, VA
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