First class of a lecture series on cancer and therapeutics

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; www.iisermohali.ac.in

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 www.rapidcityjournal.com/.../2007/032607.html
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. Cancer - incurable
www.dylanmatthews.com/images/cancer.jpg
suffering?
meddean.luc.edu/lumen/MedEd/.../MELTON/TITLE.HTM topnews.in/health/files/mouth_cancer_0.jpg hypnotiqueolmecpunch.org/Strangewomen_1.htm
students.umf.maine.edu/~delanonh/negative.html
myhealth.gov.my/.../adult/Breast_Cancer.gif taconichills.k12.ny.us/.../lungcancerpic.jpg meddean.luc.edu/lumen/MedEd/.../MELTON/TITLE.HTM

4. INTRODUCTION
Fundamental Biological aspects
of Cancer
http://southerngent.files.wordpress.com/2009/06/beat-breast-cancer.jpg
http://www.naturalhealthlibrarian.com/images/ebook_cancer.jpg http://media.merchantcircle.com/25810987/help%20key_medium.jpeg

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
http://www.cancer.org/docroot/STT/STT_0.asp
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
http://www.cancer.org/docroot/STT/STT_0.asp
the most cancer deaths www.who.int/mediacentre/factsheets/fs297/en/index.html, P.
Kanavos; Annals of Oncology 17 (Supplement 8): viii15–viii23, 2006

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.
http://www.cancer.org/docroot/STT/STT_0.asp

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.
http://www.cancer.org/docroot/home/index.asp

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.
http://www.cancer.org/docroot/home/index.asp

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. 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. 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. 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. 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. 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. 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. 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