Cancer is caused by genetic mutations from carcinogens like chemicals, radiation, and viruses. Cancer cells show uncontrolled growth, loss of contact inhibition, and altered biochemistry. Tumor markers are proteins produced by or in response to cancer that can help detect and monitor cancers. Common tumor markers include AFP for liver cancer, CEA for colorectal cancer, and PSA for prostate cancer.

1. Dr. Smita Narad (Pakhmode)
Department of Biochemistry
NKPSalve Medical College &RC
Biochemistry of Cancer

2. Purpose Statement:
By the end of the lecture, students shall be able to
define and explain etiology of cancer along with
tumor markers.

3. Learning Objectives Domain Level
1 Definition and etiology of
cancer
Types of carcinogen
Cognitive Must
know
2 Describe the biochemical
changes in cancer cells
Cognitive Must
know
3 Tumor Markers Cognitive Must
know
4 Anticancer drugs & their
mechanism
Cognitive Nice to
know

4. Questions asked so far
• Characteristics of growing cancerous cells (4M)
• Chemical Carcinogen (4M)
• Name four Chemical Carcinogen (4M)
• Protooncogenes & Oncogenes (4M)
• Oncogenes (4M)
• Tumor markers & their significance(4M)

5. Cancer
Cancrum
Arubuda
International Union Against Cancer( UICC)
Disturbance in growth characterized by excessive proliferation of cells
without apparent relation to physiological demands of organ involved.
Origin: ↑↑ Mutation of aberrant cell

6. Etiology: : Multifactorial
Geographic
India:Khangri Cancer,Oral Cancer
USA & Europe:Ca Prostate, Lung & Colorectal cancer
Occupational
Mesothelioma, Lung : Asbestos workers
Lung : Nikel worker
Skin Cancer: Ionizing radiation
Racial & Genetic
Dark skin: ↓ Melanoma
A +ve: Ca Stomach
Alcohol : Ca Esophagus, Hepatocellular Ca
Smoking: Ca Lung, Ca Urinary bladder

7. Characteristics
of tumor cells
↓ growth
control
Loss of contact
inhibition
2-5% cells are in
doubling phase
Multilayered
growth in jumbled
fashion
Malignant
transformation • Anaplasia
• Change in
alignment
• Multilayered
cells
• Angiogenesis
Sialic Acid
&
Sialysation
Metastasis
&
Secondaries
• ↑ Content of NANA
• ↑ Negative charges
• Altered signalization of
cell surface glycoprotein
Metabolic
alteration
Immortal
_Collagenase
& Stremolysin
-minimal enzyme
need
Alter iso enzymes
Lactic Acidosis
Synthesis of feat
protein
Persistent
activity of
telomerase
Loss of
apoptosis
• Loss of genes:
C fos, P53,Rb
• Altered Immune system

8. Genetic basis of Cancer
Carcinogenesis: Mechanism of induction
of tumor cells
Carcinogens: Agent that induced
carcinogenesis
Oncogenes: Regulatory Genes
Associated with the Carcinogenesis:
Types of Oncogenes:
1) proto-oncogenes: promote cell growth
2) tumor suppressor (anti-oncogenes):
genes inhibit cell growth
3)DNA repair genes
repairs DNA damage during Mitosis
4) Apoptosis mediating genes:
are genes that regulate programmed cell death

9. Carcinogenesis:
Molecular basis of Carcinogenesis
Unregulated cell
proliferation
↓ Apoptosis
Malignant Transformation

11. Chemical Carcinogen
• Act through the mutation of protooncogene &
Antioncogene
Initiator Carcinogen
• Initiate the process of
abnormal new growth
of cells
Promoter Carcinogen
• Not Carcinogenic itself
• Help initiated cells to
grow further

12. Action of
Chemical
Carcinogen:
Initiator Carcinogen
Direct Carcinogen. Indirect Carcinogen
(Methclorethamine , Beta propiolactone) (Procarcinogen)
No Metabolic Activation Metabolic Activation
Liver ,Cyt P450
Ultimate Carcinogens
Reactive electrophiles
(electron Deficient)
Interact with Neutrophil
( Damaged DNA)
Mutation in DNA
Neoplastic transformation and development of Cancer
Indirect
Carcinogen
Tobacco smoke,
Benzedine, Vinyl
Chloride,
Asbestos
Nitrosamide
compounds
Promoter Carcinogen
Helps initiated cell to proliferate
further
Ex: Phenol, Phenobarbital
Sacchrine,
Cyclamate

13. Agent Occupation Cancer Site
Ionizing radiations radon certain underground miners bronchus
X-rays, radium radiologists, radiographers skin
Radium luminous dial painters bone
Ultraviolet radiation farmers, sailors, etc. skin
Polycyclic hydrocarbons in
soot
chimney sweepers,oil workers scrotum, skin, bronchus
2-Naphthylamine; 1-naph-
thylamine
rubber workers bladder
Benzidine; 4-aminobiphenyl chemical workers bladder
Asbestos shipyard and insulation workers Mesothelioma lung
Arsenic sheep dip manufacturers, gold miners skin and bronchus
Benzene workers with glues, varnishes, etc. marrow (leukemia
Vinyl chloride PVC manufacturers liver (angio-sarcoma)
Aflatoxin B1 Food storage. Due to growth of
Aspergillus flavus (fungi)
Liver
Benzo(a)pyrene Smokers Lung
Chemical Carcinogen

14. Hepatocellular Carcinoma
Aspergillus flavus

15. Cigarette smoking is injurious to health
Your smoking is injurious to our health
NICOTINE, CO,
NO2,
CARBON SOOT
10/DAY
15% 40%
20/DAY
5%
GST

16. Anti Mutagen
• Substances which interfere tumor prevention.
• Vit A: Reverse precancerous condition
• Vit C: Protective effect
• Vit E: Antioxidants effect
Role of food as antimutagen:
Low protein & Low fat diet
Tubers beans & green leafy vegetable
Curcumin( turmeric)
Phenolic compounds Grapes/ strawberry/
Walnuts:
Green tea;
Reduces tumor production
Prevents mutation
Antimutagenic Activities

17. Radiant Energy
Ionising radiations
X-rays, β rays & 𝝲
rays
Mutagenic & Carcinogenic
Alteration in cells:
Formation of
• purine dimers in DNA
• Apurinic & Apyrimidinic sites by deletion of bases
• Single or double strands or Cross linking of DNA
• free radicals which damage DNA
Skin Cancers

18. Mechanism of biological Carcinogenesis
DNA VIRUSES
(Adenovirus, Herpes virus, Papovirus)
Alter gene expression
Inactivate tumor suppressor gene:
p53 & Rb
RNA VIRUSES
(Retrovirus type B and C)
Formation of provirus by
reverse transcriptase
De regulation of cell cycle
Inhibition of Apoptosis regulatory gene
Abormality in cell signaling pathways

19. Oncogenic Viruses
Biological Carcinogen
Virus Genome Type of Cancer
Human Papilloma Virus(HPV) DNA Ca Cervix,
Ca Nasopharynx
Epstein Bar Virus(EBV) DNA Burkitts lymphoma
Ca Nasopharynx
Human Herpes Virus (I) DNA Kaposi Sacroma
Hepatitis B Virus(HBV) DNA Hepatocellular Carcinoma
Human T cell Leukemia (Type I) RNA Human T cell Leukemia
Hepatitis C RNA Hepatocellular Ca

20. ONCOGENES
Mutation
Expression

21. Cellular oncogenes
oncogenes Virus carrying gene Oncogene
product
Subcellular
localization of
oncogene
product
Abl Ableson Leukemia Virus
in mouse
Tyrosin Kinase Plasma
Membrane
erb-B Erythroblstosis virus in
chicken
Receptor for
Epidermal growth
factor
membrane
Myc Mylocytoma Virus in
Chicken
DNA binding
Protein
Nucleus
sis Simian Sacrcoma Virus
in Monkey
Platelate derived
growth factor
membrane
Ras Rat Sarcoma GTPase Cytoplasm

22. Short arm of chromosome 17
p53
(Molecular policeman, Guardian genome,
Gatekeeper gene)
Phosphoproteins Suppress
transformational
ability of tumor
cells by oncovirus
Sever
Damaged
DNA Cells
Direct cell
commit Suicide
Apoptosis
Blocks cells
with damaged
cell division
until repair
Activate
expression of
gene that
suppress cell
proliferation
Cancers
Leukemia
Lung,
Colorectal,
Breast
Mechanism of actions of p53 tumor suppressor gene
Tumor suppressor Genes: produces products which suppresses
normal Growth & Cell division

23. Retinoblastoma
gene
Protein pRB.
Nuclear
Transcription
proteins
↓ cell proliferation
& prevent activity
of oncogene
Retinoblastoma
BRCA gene
5% in Breast Cancer
50% Familial Breast
Cancer
10-15% Ovarian Cancer
Mutation
Other Onco suppressor gene: Wilms tumor(WT), Familial Adenomatous
polyposis (FAP), Deleted in colon Cancer (DCC)
Oncosupressor Genes

24. Apoptosis
• Programmed cell death (programmed suicide)
Normal
Elimination of potentially harmful
cells &Aging cell
Implantation, organogenesis,
developmental involution
metamorphosis
Pathological
Damaged cells of DNA & proteins
Radiation, cytotoxic drugs,
Extreme temperature, hypoxia
Growth factor deprivation
P53 proteins
Apoptosis by cell
mediated lymphocyte
Mitochondrial enzyme pathway
Death receptor pathway

25. Tumor Immunology
• Immunological reactions in tumor bearing host cell.
• Altered Immune response :
• ↑levels of Oncofetal antigen
• Prevention of T cell against Cancers
• PD-1, protein indicates immune brake
AFP : Hepatoma
CEA: Colon Cancer

26. Tumor markers
• Tumor markers are usually proteins which
are produced from cancer cells or as
response to cancer
• Cancer specific
• Tissue specific
An Ideal tumor Marker
(a)highly specific to a given tumor type,
(b)provide a lead-time over clinical diagnosis
(c)highly sensitive to avoid false positive results

27. In oncology tumor markers are used:
• Screening of Cancer i.e PSA
• Monitoring & follow up i.e AFP
• Diagnosis (when biopsy is not feasible)
• Determine prognosis

28. Oncofetal antigens
AFP Hepatocellular Ca
CEA Colorectal, stomach
Hormones
calcitonin Medullary Ca of thyroid
Growth Hormone Ca of Pituitary
parathyroid hormone Liver
Prolactin Adenoma of Pitutary
hCG
Tetratoma of testes,
choriocarcioma

29. Carbohydrate markers
CA- 125 Ovarian
CA 549 Breast
Proteins
beta Microglobulin Multiple myeloma
C peptide Insulinoma
Ferritin Liver
Immunoglobulin Multiple myeloma
Enzymes
Amylase Pancreatic
Alkaline phosphatase Bone, liver
Prostatic acid phosphatase Prostate
PSA prostate
LDH
Liver, lymphoma,
leukemia

30. ANTI CANCER DRUGS
Methotrexate Folic acid analogue
6- Mercaptopurine Purine analogue
6-Thioguanine Purine analogue
Mitomycin C Antibiotic
Actinomycin Antibiotic
Vinblastin
Vincristine Alkaloids
Cisplastin Platinum compound

31. Applied aspects /clinical implication
Understanding etiology of cancer help in
Chemically synthesize Synthetic Nucleotide
Analogs which acts as Anti-tumor agents,
Antiviral agents.

32. Commonly asked questions in university
exams
Tumor markers (4M)
Protooncogenes(4M)
Biochemical changes in cancer cells(4)

33. Bibliography
1.Harper’s Illustrated Biochemistry, 8th Edi. Murray & Bender
2. Text Book of Biochemistry,5th edi. Pankaja Naik
3. Text Book of Biochemistry,8th edi. Vasudevan &
Sreekumari S

34. THANK YOU
34

35. Tumor markers cancer
Alpha Fetoprotein Hepatocellular Ca
CEA( Carcino
embryonic Ag)
Colorectal Cancer
Ca of breast, lung & Ovary
CA (Cancer Antigen
125)
Ovarian Cancer
PSA: Prostate Specific
Ag
Ca Prostate
ER/PR Ca Breast & Ca Uterus

36. Carcinogens are agents that have the ability
to initiate the formation of cancer.
Chemical Carcinogens
Physical Agents
Ionizing Radiation
Oncogenic Viruses

37. Oncogene Activation
Environmental factors
Mutations
Oncogenic viruses
Inactive Antioncogenes
CARCINOGENESIS
Diminished regulation
by Apoptosis genes

38. Mechanism
Promotors

39. Adhesion to
Tumour cell
Molecules t
Sialyl-Lewis
Shape of cells
Alteration in cell structure
Loss of contact inhibition
Loss of anchorage dependence
Alteration in permeability
properties

40. BIOCHEMICAL PROFILE
•Increased synthesis of RNA and DNA
•Decreased catabolism of pyrimidines
•Alterations in isoenzyme patterns
•Increased rate of aerobic and anerobic glycolysis
– Lactic acidosis
•Synthesis of fetal proteins – CEA
•Diminished synthesis of specialized proteins
•Inappropriate synthesis of growth factors
and hormones
•Alterations of cell surface

41. Summary
• Cancer : Abnormal excessive uncoordinated growth
• Types : Benign, Malignant
• Etiology: Chemical Carcinogens
Physical Agents
Ionizing Radiation
Oncogenic Viruses
• Tumor Markers: Cancer specific
Tissue specific

42. Acknowledgement
Department wishes to acknowledge with
thanks
• Efforts of Dr. Manju Chandankhedefor
making this LRM
• Staff of the department for content
validation
• MET department for guidance & format
validation