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The Lung Cancer Epidemic: is there anything we can do?

The Lung Cancer Epidemic: is there anything we can do?. Diana C. Márquez-Garbán. University of California, Los Angeles Division of Hematology-Oncology. Acknowledgements. National Program Excellent University EU/Slovakia Dr. Martina Nebohácová. National Program Excellent University

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The Lung Cancer Epidemic: is there anything we can do?

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  1. The Lung Cancer Epidemic:is there anything we can do? Diana C. Márquez-Garbán University of California, Los Angeles Division of Hematology-Oncology

  2. Acknowledgements National Program Excellent University EU/Slovakia Dr. Martina Nebohácová National Program Excellent University EU/Slovakia UCLA Richard J. Pietras Hermes J. Garbán Hsiao-Wang Chen Olga Weinberg Edward Garon Eugene Tsai Jeison Recinos UCLA Lung Cancer SPORE Program Dr. Steven Dubinett

  3. Global Incidence • 1.3 million deaths/year worldwide. • Lung cancer kills more people than any other cancer • Number one killer in men and second in women • 5 year survival still at 14% • Risk factors: radon, asbestos, air pollution Tobacco smoke responsible for 87% of cases of Lung Cancer

  4. Smoking and Lung Cancer: History “Phenomenal increase in the number of deaths attributed to cancer of the lung” (1922-1947) Cigarette smoking is related to Lung Cancer

  5. Death rate from lung cancer and consumption of tobacco (1900-1950) Lung Cancer Tobacco Cigarettes Doll et al. British Medical Journal (1950)

  6. Death rates from lung cancer and consumption of tobacco (1880-2000)

  7. Smoking prevalence for men in Slovakia The Tobacco Atlas, WHO, 2002

  8. Smoking prevalence for women in Slovakia The Tobacco Atlas, WHO, 2002

  9. Toxic chemicals in tobacco smoke * Nicotine – the addictive agent in tobacco smoke * Formaldehyde – used in preservation of laboratory specimens * Ammonia – used in toilet cleaner * Hydrogen Cyanide – used in rat poison * Acetone – used in nail polish remover * Carbon monoxide - found in car exhaust * Tar - particulate matter in cigarette smoke * Toluene - found in paint thinners * Phenol – used in fertilisers.1,2

  10. Smoking Damages Virtually Every Part of the Body Smoking

  11. Second-Hand Smoke Second-hand smoke also does

  12. Smoker’s lung Lung Cancer Normal and Smoker’s lung Normal

  13. Tobacco Is a Risk Factor for 6 of the World’s 8 Leading Causes of Death

  14. Lung Cancer Facts Myth: Lung cancer is a man’s disease. Fact: The incidence of lung cancer in men has been leveling off in recent years. In women, however, the incidence is rising rapidly.

  15. Lung cancer among women at epidemic proportions Age-adjusted death rates for lung cancer and breast cancer among women, US, 1930-1997. 600% increase in death rate in 50 years

  16. 1960: First brand specifically manufactured for women Virginia Slims: “You've come a long way, baby" "It's a woman thing” "Find Your Voice”

  17. Virginia Slims remembers when a woman carried more weight than a man

  18. Marketing campaigns targeted women with the social pressures they face

  19. Women who smoke like men, die like men

  20. Classification • Non-Small Cell (~85%): • Adenocarcinoma: 40% of all cases • Most common among women • Squamous • Large Cell • Small Cell • Related to Smoking • More Aggressive than NSCLC

  21. Lung Cancer Symptoms Persistent cough Hoarseness Change in color (blood) or amount of sputum Recurrent pneumonia, bronchitis Diagnosis Radiology: Chest X-ray, CT scan, MRI scan, PET scan Biopsy: Needle, bronchoscope-directed, open surgical

  22. CT Scan Lung Cancer X-ray

  23. Staging and Treatment of Lung Cancer Stage IEarlySurgery Stage II +/- Radiation Stage III +/- Chemotherapy Stage IV AdvancedChemotherapy

  24. Non-small Cell Lung Cancer • Staging: Estimate prognosis Guide treatment decisions • 70% present with advanced locoregional or metastatic involvement Stage IIIA, IIIB, or IV 5 year survival 1-25% Ginsberg RJ, et al. Cancer: Principles and Practices of Oncology. 5th ed. 1997;858-911.

  25. Lung Cancer: One Name, Many Diseases • Heterogenous disease: • Smokers vs. non-smokers • Women vs men • Epidemiologic findings suggest women more susceptible than men to the effects of tobacco smoke (Henschke C, JAMA 2006) • Women develop the disease at an earlier age and with less reported tobacco exposure than men • Among non-smokers, women are particularly vulnerable to lung cancer (80% of cases) ? • Women: increasing incidence

  26. Do Hormones Influence Lung Cancer Progression? • Estrogen contributes to normal lung development • Association of estrogen levels and lung cancer survival • Serum estrogen elevated in women with lung cancer compared to similar age without lung cancer(Tiuriunova et al, 1986) • Hormone replacement therapy and lung cancer survival • Lung epithelium express ER- and ER- • Receptors are active • Lung epithelium produce estrogen (via aromatase) • Estrogen stimulates proliferation in vitro and in vivo

  27. Cell functions and alterations In vitro: cell models In vivo: tumor xenografts in mice

  28. Estrogen Receptor : Membrane and Nuclear Actions in Tumor Growth Regulation Gruber et al. New Engl J Med (2002)

  29. Antibodies to ERa and ERb React with Nuclei and Membrane-Cytoplasmic Sites in NSCLC Cells in vitro ERa ERb Non-Permeabilized FITC-conjugated secondary antibody to primary C-terminal or N-terminal ER antibodies Permeabilized

  30. Estrogens stimulate growth of non-small cell lung cancer Estrogen enhances NSCLC proliferation several-fold (Stabile et al. 2002, 2004; Pietras et al. 2005)

  31. Estrogen Receptor a and Estrogen Receptor b: Expression in NSCLC from the Clinic Extra-nuclear localization Nuclear localization ER-alpha ER-beta

  32. Src Estrogen signaling interacts with EGFR/HER pathways EGFR/HER estrogen shc Faslodex (ICI 182,780) ER TKI (Erlotinib/Gefitinib) MNAR ER ARO cytoplasm MAPK/AKT ER ER Ligand-independent Ligand-dependent P ER SRC-3 Growth Survival Angiogenesis TF ER ER nucleus

  33. Activated Estrogen Receptor Alpha is present in NSCLC tumor specimens S118 S167 A/B C D E F N C Estrogen receptor alpha serine phosphorylation ER-phospho S118 ER-phospho S167 80% (16/20 adeno) 88% (15/17 adeno)

  34. Antiestrogen Faslodex blocks estrogen-induced growth tumor xenograft nude mice

  35. NSCLC Tissue Microarray Standard Histologic Block Tissue Cores

  36. Lung tumor microarray: tumor aromatase and survival Low Aromatase Low Aromatase (blue curve) High Aromatase High Aromatase (red curve) Survival probability in postmenopausal women with Stage I/II NSCLC and tumor aromatase expression (P<0.038)

  37. What can we do? Tobacco is the world’s single most avoidable cause of death

  38. Most Countries Have Not Implemented Effective Tobacco Control Policies WHO Report on the Global Tobacco Epidemic, 2008

  39. In the 20th century the tobacco epidemic killed 100 million people worldwide During the 21st century, it could kill 1,000 million WHO Report on the Global Tobacco Epidemic, 2008

  40. We must become the change we want to see Mahatma Gandhi (1869-1948)

  41. Lung Cancer Facts 90% of new smokers begin as teenagers; one third of these new smokers will eventually die of tobacco related diseases.

  42. 1970-today: advertising with so-called “light” and “low-tart” Tobacco companies use lies: cigarettes with “reduced risk”

  43. Risks men are not exposed to: Birth Control Pill- Increased risk of heart attack and stroke Mother to be- baby likely to be under weight Smoking reduces fertility Reach menopause earlier than non smokers Higher risk of osteoporosis Increased risk of cervical cancer Stopping: - Improves weight of baby - After 2y risk of HA and stroke decrease

  44. Myths about smoking It won't happen to me. It’s not like I am hurting anyone but myself. I'm not hooked. I can stop anytime I want. 4 Sure I smoke, but at least I don't do drugs, have unsafe sex, or get drunk. 5 It’s better to smoke because if I quit, I’m going to get fat. 6 I smoke "light" cigarettes, so I won't get hurt as much. 7 I've tried to quit, but I can't.

  45. Second Hand Smoke It causes heart disease and lung cancer Exposed at home or work- Increased risk of lung cancer and heart disease People with heart disease at increased risk of HA Even brief exposure can be dangerous In children: • Respiratory symptoms in children and slows the growth of their lungs • Sudent infant death syndrome, acute respiratory infections, ear problems and worsens asthma

  46. Advertisement from Australian campaign to prevent smoking in teenagers Every cigarette is doing you damage

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