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

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.,

The Molecular Biology of the Cell 4th Edition (2002)
Cancer therapy
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,
Springer. ISBN 978-3-540-74385-9 (2009). Yi Lu, R. I.
The Future of Cancer Research
Mahato, Pharmaceutical perspectives of cancer
therapeutics, Springer. ISBN 978-1-4419-0130-9 (2009).
Recent papers study and Discussions

www.dylanmatthews.com/images/cancer.jpg

meddean.luc.edu/lumen/MedEd/.../MELTON/TITLE.HTM

myhealth.gov.my/.../adult/Breast_Cancer.gif

Cancer - incurable
suffering?

topnews.in/health/files/mouth_cancer_0.jpg

taconichills.k12.ny.us/.../lungcancerpic.jpg

hypnotiqueolmecpunch.org/Strangewomen_1.htm

students.umf.maine.edu/~delanonh/negative.html
meddean.luc.edu/lumen/MedEd/.../MELTON/TITLE.HTM

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

Cancer Statistics
US Mortality, 2006
Rank

No. of deaths % of all deaths

Cause of Death

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
the most cancer deaths

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

www.who.int/mediacentre/factsheets/fs297/en/index.html, P.
Kanavos; Annals of Oncology 17 (Supplement 8): viii15viii23, 2006

Change in US Death Rates from 1991 to 2006

400

Rate Per 100,000

1991
313.0

2006

300

200.2

200

100

215.1

180.7

63.3

43.6

34.8

17.8

Heart diseases

Cerebrovascular
diseases

Influenza &
pneumonia

Cancer

Why Cancer is Potentially Dangerous?

Sources: American Cancer Society home page. 1950 Mortality Data - CDC/NCHS, NVSS, Mortality Revised.

February 26, 2001

2006 Mortality Data: US Mortality Data 2006, NCHS, Centers for Disease Control and Prevention, 2009.
http://www.cancer.org/docroot/STT/STT_0.asp

2009 Estimated US Cancer Deaths

Men
292,540

Lung & bronchus

30%
Prostate
9%
Colon & rectum
9%
Pancreas
6%
Leukemia
4%
Liver & intrahepatic
4%
bile duct
Esophagus
4%
Urinary bladder
3%
Non-Hodgkin lymphoma 3%
Kidney & renal pelvis
3%
All other sites
25%

Have you heard of heart cancer?

Source: American Cancer Society home page.
http://www.cancer.org/docroot/home/index.asp

Women
269,800
26%
15%
9%
6%
5%
4%
3%
3%
2%
2%
25%

Lung & bronchus

Breast
Colon & rectum
Pancreas
Ovary
Non-Hodgkin lymphoma
Leukemia
Uterine corpus
Liver & intrahepatic
bile duct
Brain/ONS
All other sites

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

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?

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

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

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

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
Paul Graphics

Fourth/ subsequent
Uncontrolled growth
mutation

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
Normal

Paul Graphics

Hyperplasia

Mild-dysplasia

Cancer (severe
Cancer (invasive)
dysplasia)

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

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