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Cancer Introduction Class


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First class of a lecture series on cancer and therapeutics

Cancer Introduction Class

  1. 1. This presentation is for teaching purpose only Cancer and Therapeutics Dr. Manash K. Paul Department of Biology Indian Institute of Science Education and Research Mohali;
  2. 2. Broad areas of Lectures on Cancer and Therapeutics Introduction Cell and Molecular Biology of Cancer Development Signal Transduction and Cell Growth Regulation Genetic Pathways Genomic Stability in Cancer Dysregulation of Cell Cycle Control Apoptosis and cancer Role of respiration and cancer Warburg effect and glucose metabolism The immune system and tumorigenesis Stem Cells and Cancer stem cells Metastasis and Angiogenesis Cancer Diagnosis and Pathology Textbook & Readings: As a general background source Alberts B. et al., Cancer therapy The Molecular Biology of the Cell 4th Edition (2002) Garland Science Press, ISBN 0-8153-3218-1 is Principles of Cancer Chemotherapy, Drug discovery recommended. As a detailed source Robert A. Weinberg, The Biology of Cancer Garland Science Press, ISBN Rational Design of Cancer Therapeutics 0-8153-4078-8 (2007). Lauren Pecorino, Molecular Biology of Cancer, Oxford University Press. ISBN Drug Delivery 978-0-19-921148-7 (2008). M. Molls, P. Vaupel, C. Nieder, M.S. Anscher. The impact of tumor biology on Models to study cancer cancer treatment and multidisciplinary strategies, The Future of Cancer Research Springer. ISBN 978-3-540-74385-9 (2009). Yi Lu, R. I. Mahato, Pharmaceutical perspectives of cancer Recent papers study and Discussions therapeutics, Springer. ISBN 978-1-4419-0130-9 (2009).
  3. 3. Cancer - incurable suffering?
  4. 4. INTRODUCTION Fundamental Biological aspects of Cancer
  5. 5. Cancer Statistics US Mortality, 2006 Rank Cause of Death No. of deaths % of all deaths 1. Heart Diseases 631,636 26.0 2. Cancer 559,888 23.1 3. Cerebrovascular diseases 137,119 5.7 4. Chronic lower respiratory diseases 124,583 5.1 5. Accidents (unintentional injuries) 121,599 5.0 6. Diabetes mellitus 72,449 3.0 7. Alzheimer disease 72,432 3.0 8. Influenza & pneumonia 56,326 2.3 Burden of Cancer in the World 15 million new cases of cancer by 2020 12 million deaths from cancer by 2020 Lung, stomach, liver, colon and breast cancer cause the most cancer deaths, P. Kanavos; Annals of Oncology 17 (Supplement 8): viii15–viii23, 2006
  6. 6. Change in US Death Rates from 1991 to 2006 400 Rate Per 100,000 1991 313.0 2006 300 215.1 ? 200.2 200 180.7 100 63.3 43.6 34.8 17.8 0 Heart diseases Cerebrovascular Influenza & Cancer diseases pneumonia Why Cancer is Potentially Dangerous? Sources: American Cancer Society home page. 1950 Mortality Data - CDC/NCHS, NVSS, Mortality Revised. February 26, 2001 6 2006 Mortality Data: US Mortality Data 2006, NCHS, Centers for Disease Control and Prevention, 2009.
  7. 7. 2009 Estimated US Cancer Deaths Men Women 292,540 269,800 • Lung & bronchus 30% 26% Lung & bronchus • Prostate 9% 15% Breast • Colon & rectum 9% 9% Colon & rectum • Pancreas 6% 6% Pancreas • Leukemia 4% 5% Ovary • Liver & intrahepatic 4% 4% Non-Hodgkin lymphoma bile duct 3% Leukemia • Esophagus 4% 3% Uterine corpus • Urinary bladder 3% 2% Liver & intrahepatic • Non-Hodgkin lymphoma 3% bile duct • Kidney & renal pelvis 3% 2% Brain/ONS • All other sites 25% 25% All other sites Have you heard of heart cancer? Source: American Cancer Society home page.
  8. 8. What is Cancer ? How are cancer named ? Cancer - diseases, in which cells divide abnormally without control and are able to invade other tissues Most cancers are named for the organ or type of cell in which they start Source: American Cancer Society home page.
  9. 9. Cancer types ? Carcinoma - cancer of skin or in tissues that line or cover internal organs. Sarcoma - cancer of bone, cartilage, fat, muscle, blood vessels, or other connective or supportive tissue. Leukemia - cancer of blood-forming tissue such as the bone marrow and causes large numbers of abnormal blood cells. Lymphoma and myeloma - cancers of the cells of the immune system. Central nervous system cancers - cancers of the tissues of the brain and spinal cord. Have you heard of cancer of RBC?
  10. 10. Tumors ? Benign tumors are not cancer: Benign tumors are generally slow growing expansive masses often with a “Pushing margin” and enclosed within a fibrous capsule. Malignant tumors are cancer: Malignant tumors are usually rapidly growing, invading local tissue and spreading to distant sites. Malignant and Benign tumors Benign tumor Malignant tumor/ cancer cells can grows locally spread by invasion and metastasis Time Paul Graphics
  11. 11. Cancer history ? Hippocrates used the Greek words, carcinos and carcinoma to describe tumors, thus calling cancer “karkinos” Well known to ancient Egyptians and to succeeding civilizations. The world's oldest documented case of cancer hails from ancient Egypt, in 1500 b.c. Treated by cauterization, a method to destroy tissue with a hot instrument called "the fire drill” Rudolph Virchow in late 19th century recognized that even cancerous cells were derived from other cells Karl Thiersch (German): cancer spread through malignant cells Cancer chemotherapy was started by Louis Goodman and Alfred Gilman in the 1940s with the use of nitrogen mustards Sidney Farber tageted cancer using folic acid antagonist as drugs
  12. 12. The Etiology of Cancer Viruses (papilloma, Epstein-Barr, hepatitis B, retrovirus) Radiation exposure Environmental/ industrial carcinogens * Asbestos * Aromatic amines * Bischloromethyl ethers * Beta-naphthalene and benzedrine * Polycyclic hydrocarbons * Drug-induced cancers (alkylators such as melphalan and cyclophosphamide) * Nickel * Vinyl chloride * Isopropyl alcohol * Diet and nutrition Tobacco and alcohol consumption Immunodeficiency syndromes: HIV is associated with Kaposi's sarcoma, non-Hodgkin's lymphoma Genetic susceptibility syndromes
  13. 13. Origin of Cancer Cells grow and divide in a controlled way to produce more cells The genetic material (DNA) of a cell can become damaged or changed, producing mutations that affect normal cell growth and division Extra cells thus formed may form a mass of tissue called a tumor. Formation of Cancer Normal cell Normal cell division Apoptosis / programmed cell death Cell damage - no repair Cancer cell division Cell damage - no repair Normal cell No Apoptosis First mutation Second mutation Third mutation Fourth/ subsequent Paul Graphics mutation Uncontrolled growth
  14. 14. Carcinogenesis Carcinogenesis: A Process by which normal cells gets transformed into cancer cells. Hyperplasia: Abnormal proliferation of normal cells within a tissue and may result in the enlargement of an organ or formation of a benign tumor Dysplasia: Condition characterized by an abnormal expansion of immature cells within a tissue,suggestive of an early neoplastic process. Neoplasia: Abnormal, uncoordinated proliferation of cells, usually causes a lump or tumor. Neoplasms may be benign, pre-malignant or malignant. Carcinogenesis Mild-dysplasia Cancer (severe Normal Hyperplasia Cancer (invasive) dysplasia) Paul Graphics
  15. 15. Clinical symptoms or signs of cancer Cancer normally presents with certain signs or symptoms and are as follows: Alteration in eating habit Loss of appetite Change in bowel habit The presence of a lump at any site The appearance of bleeding Unexplained recurrent pain Recurrent fever Unexplained weight loss Repeated infections which do not clear with treatment
  16. 16. Nature of Cancer 1. Normal tissues are the source of Tumors Tumors are made up of cells Continuity between normal and cancer tissues Undergoes metastasis 2. Tumors arise from many specialized cell types throughout the body 3. Tumors are monoclonal in nature Monoclonality versus Polyclonality Cancer occurs with different frequencies in different populations ? When a breast cancer cell metastasizes to lung. What does it form there a lung/ breast cancer ? Can you plan an experiment to highlight on the monoclonality vs polyclonality issue of cancer? What percentage of cancers are inheritable? Can cancer be caused by a bacteria? Thank you