Cancer is characterized by uncontrolled cell growth and the spread of abnormal cells. It is caused by somatic mutations and disruptions to oncogenes and tumor suppressor genes. Many factors like environment, diet, smoking, and alcohol consumption can influence cancer risk. Researchers are studying the cancer genome to better understand carcinogenesis at the molecular level and identify new targeted therapies.

1. An introduction to Cancer
SALMAN UL ISLAM
2014-11-05
2013298039
Kyungpook National University

2. What is Cancer?
 Cancer is a group of diseases characterized by
unregulated cell growth and the invasion and
spread of cells from the site of origin, or primary
site, to other sites in the body.

3. Benign vs Malignant tumors
Benign tumors Malignant tumors
 Slow growing
 Capsulated
 Non-invasive
 Do not metastasize
 Well differentiated
 Suffix “oma” e.g. Fibroma
 Fast growing
 Non-capsulated
 Invasive & infiltrate
 Metastasize
 Poorly differentiated
 Suffix “Carcinoma” or
“Sarcoma”
http://medicinembbs.blogspot.kr/2011/02/neoplasia.html

4. Classification of cancer
 There are more than 100 types of cancer. These
are classified on the basis of tissue of origin.
 Carcinomas: Cancers of epithelial cells. They
constitute approximately 85% of all cancers.
 Sarcomas: Cancers of mesoderm cells (e.g. bone,
muscle).
 Adenocarcinomas: Cancers of glandular tissue (e.g.
breast).

5. Classification of cancer

6. “Hanahan & Weinberg defined” Hallmarks of
cancer

7. Cancer usually causes somatic mutations
 Somatic cells: All the body cells except the
reproductive (germ) cells.
 Germ cells: Either the egg or the sperm cell; a
reproductive cell.
 Almost all of the mutations identified in tumor
cells are somatic mutations. These mutations are
not passed on to the next generation.
 Only germline mutations will be passed on to off-spring.

8. Cancer usually causes somatic mutations

9. Normal body processes regulate body net
cells number
 Cell proliferation, differentiation and apoptosis
regulate overall net cell number in an individual.
Total 9 cells
4 cells divided
4 cells died
1 cell differentiated
Total remaining
cells= 9
Apoptosis is blocked
in 1 cell
5 cells divided
3 cells died
1 cell differentiated
Total remaining
cells= 11

10. Oncogenes and tumor suppressor genes
regulate cancer
 Oncogene: It is the gene mutated such that its
protein product is produced in higher quantities,
or has increased activity and therefore initiate
tumor formation. It sometimes produces a growth
factor receptor that is always in the “ON” state.

11. Oncogenes and tumor suppressor genes
regulate cancer
 Tumor suppressor gene: This gene codes for
proteins that play a role in inhibiting both growth
and tumor formation.

12. Oncogenes and tumor suppressor genes
regulate cancer
Knudson’s
two-hit
hypothesis

13. Influential factors in human carcinogenesis
 Factors that play an important role in
carcinogenesis include:
 Environment
 Reproductive life
 Diet
 Alcohol
 Smoking

14. Influential factors in human carcinogenesis
 Environment: Environmental agents were first
correlated with specific cancers in 1775 by a British
surgeon.
 Incidence of nasal and scrotal cancer is high in
chimney sweeps.
 Unprotected exposure to sun leads to skin cancer.

15. Influential factors in human carcinogenesis
 Reproductive life: Cancer has a great relation with reproductive life.
 Women having children have a reduced risk of breast cancer. The
risk is higher in Nuns.
 Nuns have a low incidence of cervical cancer, which is caused by
sexually transmitted human papillomaviruses.
 Kaposi’s sarcoma, which requires immunosuppressive conditions
(AIDS) is predominant in Kenyan males.

16. Influential factors in human carcinogenesis
 Diet: It is one of the most influential factors of cancer.
 Stomach cancer is a predominant cancer in the Japanese
population and a minor cancer in the population of the
USA.

17. Influential factors in human carcinogenesis
 Alcohol: Chronic alcohol drinking increases the risk of cancer
of the mouth, esophagus, and breast, and probable evidence
for increased risk of liver cancer.
 Daily alcohol intake should not exceed 28g (approx. ¼ of a
bottle of wine).
Genetics and alcoholism. Nature Reviews

18. Influential factors in human carcinogenesis
 Smoking: Smoking causes lungs cancer; the main
cancer worldwide. It is also implicated in
pancreatic, bladder, kidney, mouth, stomach, and
liver cancer.

19. Age-adjusted cancer death rates, USA,
1930-2010

20. Principles of Cancer therapies
 Surgery was the earliest strategy used against
cancer. It is not precise as cancer cells spread from
the primary site.
 Chemotherapy is preferred, either for cytostatic or
cytotoxic effect.
 The ultimate goal of chemotherapy is to damage
the DNA for inducing apoptosis in cancer cells.
 Chemotherapeutic agents having higher value of
therapeutic index are considered safe.

21. Therapeutic index
 Therapeutic index refers to the relationship between toxic and
therapeutic dose.
 Where: TD50 is the dose of drug that causes a toxic response in 50%
of the population and ED50 is the dose of drug that is
therapeutically effective in 50% of the population.

22. Clinical Trials for new anti-cancer drugs
 Clinical trials are required for testing the new
drugs in humans.
CERN Foundation, Collaborative Ependymoma Research Network, ohio

23. Single-blind and double-blind study
 Single blind study: Patients don’t know whether they are
taking treatment or placebo (control dosage forms).
 Double blind studies: Both, patient and doctor, are in dark.

24. Important molecular targets for anti-cancer
drugs
 There are several families of “star players” in the
story of carcinogenesis to be targeted.
 These interconnect many pathways and can exert
several effects in response to a specific signal.

25. Protein kinases and Ras protein

26. p53 and Retinoblastoma gene (Rb)

27. Cancer genome
 The sequencing and mapping of human genome has
paved the way of cancer genomics.
 Learning the difference between genome of cancer and
a normal cell will have a great contribution in designing
more powerful and specific drugs.
 International Cancer Genome Consortium (ICGC) is
trying to characterize at least 50 classes of cancer,
creating an open access to the entire research
community.
 The international SNP Map Working Group is anlazing
single nucleotide polymorphism (SNPs).
 It will help in identifying mutations within the genome
that may be linked with cancer.

28. Summary
 Cancer is the uncontrolled and unregulated
growth of cells which metastasize throughout
the body.
 Cancer is a genome disease at the cellular
level.
 Changes in lifestyle can affect cancer risk.
 Protein kinases are important molecules in
carcinogenesis.
 Cancer genomics is being used to define
molecular targets for tumor-specific effects.