IMPACT OF DECLINING OXYGENATION Anatomical 02 ? The body’s oxygen levels are naturally and highly variable1 When does declining oxygenation begin to have a pathological impact? Different degrees of hypoxia can lead to very different impacts on cell metabolism— especially for tumor cells.2,3 ~2%-6%* 1.25%-10%* PHYSIOLOGICAL HYPOXIA3 NORMOXIA4 <2%* † 0%* TUMOR HYPOXIA3 ANOXIA4 Hypoxic tumor areas Anoxic tumor areas Severely limited O2 No measureable O2 O2-deprived tumor cells adapt to survive4 ost cells enter immediate cell M cycle arrest, bringing cellular proliferation to a halt4,6 Adaptation leads to increased tumorigenic capacity5 Cell death pathways activated4 ecreased proliferation increases D resistance to many cytotoxics and radiation4 *Oxygen levels vary among different healthy and tumor tissues. † Median tumor oxygen level. > Get more insights on HypoxiaExposed.com References: 1. Carreau A, El Hafny-Rahbi B, Matejuk A, Grillon C, Kieda C. Why is the partial oxygen pressure of human tissues a crucial parameter? Small molecules and hypoxia. J Cell Mol Med. 2011;15(6):1239-1253. 2. Vaupel P, Mayer A. Hypoxia in cancer: significance and impact on clinical outcome. Cancer Metastasis Rev. 2007;26(2):225-239. 3. McKeown SR. Defining normoxia, physoxia and hypoxia in tumours—implications for treatment response. Br J Radiol. 2014;87(1035):20130676. 4. Luoto KR, Kumareswaran R, Bristow RG. Tumor hypoxia as a driving force in genetic instability. Genome Integr. 2013;4(1):5. 5. Vaupel P, Harrison L. Tumor hypoxia: causative factors, compensatory mechanisms, and cellular response. Oncologist. 2004;9(suppl 5):4-9. 6. Höckel M, Vaupel P. Tumor hypoxia: Definitions and current clinical, biologic, and molecular aspects. J Natl Cancer Inst. 2001;93(4):266-276. EMD Serono, Inc. is a subsidiary of Merck KGaA, Darmstadt, Germany © EMD Serono, Inc. US-NON-0215-0027 March 2015 JOB # / JOB NAME: 24016_EMDG_Infographic_8.5x11_M.indd NOTES / INSTRUCTIONS: SCALE %: ROUND 1 STUDIO COPYWRITER TRAFFIC COPY EDITOR TODAY’S DATE / TIME: 4/10/15 LIVE: 8x10.5 CS MANAGER PROOFER INTERNAL REVIEW DUE: 4/15/15 TRIM: 8.5x11 PLANNING PRODUCER BLEED: n/a CLIENT REVIEW DUE: CD INTERACTIVE PUBLICATION DUE: 4/20/15 FLAT: ASSOC. CD ACCOUNT PUB DATE / ISSUE: n/a FOLDED: AD ACCT SUP.