Biochemistry of Cancer

2. Biochemistry of Cancer
Ashok Katta

3. What Is Cancer?

5. Cancer
• Cancer is uncontrolled growth and
Cell proliferation results in a mass
(tumor) that invades neighboring
tissues and may metastasize to more
distant sites.
• Some cancers, however, such as
blood cancers, do not form tumors.
Cancer is one of the most common and
severe problems of clinical medicine.

8. • Tumors can be of 2 major types:
• Benign tumors are generally slow growing
expansive masses often with a “Pushing
margin” and enclosed within a fibrous capsule.
Benign tumors are not cancer.
• Malignant tumors are usually rapidly
growing.
• invading local tissue and spreading to
distant sites.
Malignant tumors are cancer.

9. Characteristics of cancer cells
 Dedifferentiated;
 Less adherent;
 Loss of cell cycle control;
 Tissue invasion and metastasis;
 Evading apoptosis;
 Insensitivity to antigrowth factor;
 Increased mutation rate;
 Induce local blood vessel formation
(angiogenesis).

10. BIOCHEMICAL CHANGES IN
CANCER CELLS AND NORMAL CELLS
Loss of contact inhibition
Growing cells forms multilayer
Increased Synthesis of RNA & DNA
Decreased catabolism of pyrimidine
glycolysis leads to lactic acidosis
Synthesis of fetal protein
Increase in growth factor secretion
Increase in oncogene expression
Loss of tumor suppressor genes
Contact inhibition
Forms single layer
Synthesis of RNA & DNA is normal.
catabolism of pyrimidine also normal
Mostly aerobic glycolysis
Oncogene expression is rare
Intermittent or co-ordinated growth
factor secretion
oncogene expression is absent
Presence of tumor suppressor genes
NORMAL CELLS
Normal
cell
Few
mitoses
Frequent
mitoses
Nucleus
Blood vessel
Abnormal
heterogeneous
cells
CANCER CELLS

11. Nomenclature of Cancer
Lung
Breast (women)
Colon
Bladder
Prostate (men)
Some common
sarcomas:
Fat
Bone
Muscle
Lymphomas:
Lymph nodes
Leukemias:
Bloodstream
Some common
carcinomas:

12. Naming Cancers
Prefix Meaning
adeno- gland
chondro- cartilage
erythro- red blood cell
hemangio- blood vessels
hepato- liver
lipo- fat
lympho- lymphocyte
melano- pigment cell
myelo- bone marrow
myo- muscle
osteo- bone
Cancer Prefixes Point to Location

13. Naming Cancers
Prefix Meaning
adeno- gland
chondro- cartilage
erythro- red blood cell
hemangio- blood vessels
hepato- liver
lipo- fat
lympho- lymphocyte
melano- pigment cell
myelo- bone marrow
myo- muscle
osteo- bone
Cancer Prefixes Point to Location

14. Loss of Normal Growth Control
Cancer
cell division
Fourth or
later mutation
Third
mutation
Second
mutation
First
mutation Uncontrolled growth
Cell Suicide or Apoptosis
Cell damage—
no repair
Normal
cell division

15. Example of Normal Growth
Cell migration
Dermis
Dividing cells in
basal layer
Dead cells
shed from
outer surface
Epidermis

16. The Beginning of Cancerous Growth
Underlying tissue

17. Tumors (Neoplasms)
Underlying tissue

18. Invasion and Metastasis
3
Cancer cells reinvade
and grow at new
location
1
Cancer cells invade
surrounding tissues and
blood vessels
2
Cancer cells are
transported by the
circulatory system to
distant sites

19. Malignant versus Benign Tumors
Malignant (cancer) cells
invade neighboring tissues,
enter blood vessels, and
metastasize to different sites
Time
Benign (not cancer) tumor
cells grow
only locally and cannot spread
by invasion or metastasis

20. Why Cancer Is Potentially Dangerous
Melanoma cells
travel through
bloodstream
Melanoma
(initial tumor)
Brain
Liver

22. What Causes Cancer?
Some viruses or bacteria
Heredity
Diet
Hormones
RadiationSome chemicals

23. Etiology of Cancer
•Genetic factors
•hormonal
•Racial & geographic factors
•Environmental factors
•Chemical factors
•Age
•Sex

24. Heredity Can Affect Many
Types of Cancer
Inherited Conditions That Increase Risk for Cancer

25. Mutagens / Carcinogens
•Any substance which increase rate of
mutation
•All mutagens are carcinogens.
•Examples are……
• Radiations like X-ray, UV-ray, gamma ray
• Chemicals like benzopyrenes, Aflatoxins
• Hormones like estrogen

26. Industrial Pollution
Some of the chemical Carcinogens in the Workplace

27. Tobacco Use and Cancer
Some Cancer-Causing Chemicals in Tobacco Smoke

28. Viruses and Cancer
• Viruses promoting human cancer. These include
both DNA viruses and retroviruses, type of RNA
viruses.
Tumor Viruses

29. DNA Tumor Viruses
•Viruses can contribute to cancer by
inserting their DNA into a chromosome in a
host cell.
•Insertion of the virus DNA directly into a
proto-oncogene may mutate the gene into
an oncogene, resulting in a tumor cell.

30. RNA Tumor Viruses
• The ability of retroviruses to promote cancer
is associated with the presence of oncogenes
in these viruses.
• An example of this is the normal cellular c-sis
proto-oncogene, which makes a cell growth
factor. The viral form of this gene is an
oncogene called v-sis. Cells infected with the
virus that has v-sis overproduce the growth
factor, leading to high levels of cell growth
and possible tumor cells.

31. Cancer Genes
•Proto-oncogenes – normally promote normal
cell growth; mutations convert them to
oncogenes.
•Tumor suppressor genes – normally restrain cell
growth; loss of function results in unregulated
growth.
•Mutator or DNA repair genes – when faulty,
result in an accumulated rate of mutations.

32. Proto-oncogenes
• Proto-oncogenes are normal genes.
• These code for proteins that help to regulate
cell growth and differentiation. These are …
Growth factor,
Growth factor receptor,
Transcription factors and
Other proteins involved in proliferation of cell.
• Mutation of Proto-oncogenes leads to abnormal
production of these proteins that causes
abnormal growth.
• Excessive or inappropriate expression of these
genes can also causes abnormal growth.

34. Tumor Suppressor genes
Tumor Suppressor genes are normal genes.
These genes switch off cell proliferation.
These genes normally suppresses tumour
formation.
Mutation or deletion of these genes leads to
the loss of their function result in malignant
transformation.
Example are….
Retinoblastoma gene (RB gene)
P53 gene

37. Balance between factors stimulating and
inhibiting cell growth
Tumor
suppressor
inhibitors
Proto-
oncogenes
stimulators
Tumour
suppressor
Proto-
oncogenes

38. Oncogenes
Oncogenes or tumor genes are genes with
potential properties for the induction of
neoplastic transformation
Oncogenes are genes able to produce cancer
when overexpressed, amplified, or mutated.
Most oncogenes are mutated forms of normal
genes, called proto-oncogenes.
Proto-oncogenes are activated to oncogenes by
various mechanisms….
Point mutation,
Promoter and enhancer insertion,
Chromosomal translocation and
Gene amplification.

40. Some oncogenes & their related cancer
Oncogene Type of Cancer
Gene
modification
Ab1 Chronic myeloid leukemia Translocation
Myc
Burkitt's lymphoma
Small cell lung cancer
Translocation
Amplification
L-myc Small cell lung cancer Amplification
N-myc Neuroblastoma Amplification
Ras Bladder cancer Mutation
K-ras Colon cancer Mutation
N-ras Acute myeloid leukemia Mutation

42. --- Physiological cell death
--- Cell suicide
--- Cell deletion
--- Programmed cell death
APOPTOSIS
Cells are born, live for
a given period
of time and then die

43. WHERE can APOPTOSIS be ENCOUNTERED ?
... Growth of Embrio
... Tissue Homeostasis
... Immunology
... Chronic viral diseases
... Neurodegenerative diseases
... Reperfusion injury
... Insuline-dependent Diabetes
... Atheroschlerosis
... Miyokard Infarction
... AIDS
... Development and Treatment of Malignancies

44. GENERAL FEATURES OF APOPTOSIS
• ... Occupation of death receptors
• ... Dimerization of Bcl-2 family members
• ... Release of cytochrome c
• ... Activation of caspases
• ... Activation of DNase
1) A number of activities take place

45. Cancer Detection and Diagnosis
We will see in next class…