Cancer biochemistry involves biochemical alterations in cancer cells. Specific objectives include listing protooncogenes and tumor suppressor genes, and explaining their roles and mechanisms of action. Protooncogenes become oncogenes through activation mechanisms like mutations. Tumor suppressor genes like p53 regulate cell proliferation and their mutation leads to cancer. Cyclins and cell cycle phases are also discussed. Standard cancer treatments include surgery, radiotherapy, and chemotherapy using antimetabolite drugs. Tumor markers can be used for cancer diagnosis, prognosis, localization, and treatment monitoring and are classified based on their type.

1. Cancer
Biochemistry

2. Specific learning objectives
1. List the biochemical alterations in cancer cells
2. Explain what are protooncogenes?
3. Explain mechanisms by which they are activated to
cancer-producing oncogenes.
4. List the tumor suppressor gene.
5. Explain the mechanism of action of p53 gene product
6. List the functions of cyclins
7. List the antimetabolites and mention their uses
8. Say what are Tumor markers? Classify tumor markers
and mention their use.

3. What is Cancer ?
 Derived from Latin word ‘cancrum’ meaning crab.
 It is a group of diseases characterised by uncontrolled
cell division leading to the growth of abnormal tissue /
tumor.

4. Cell Proliferation
 Cell multiplication (proliferation) - normal physiologic process
 response to injury
 immune responses
 to replace cells that have died
 to replace cells that have been shed as a part of their life cycle
(eg: skin, mucous membrane of GI tract, etc.,)
 Kept at balance
 Impairment of this balance leads to cancer

5. Oncology
 Oncology branch of medicine deals with etiology,
diagnosis, treatment and prevention of cancer.
 Onco is a Greek word meaning tumor
.

6. Types of Tumor
 The uncontrolled and rapid proliferation of cells can lead to
either benign tumor or malignant tumor (cancer).
 Benign tumors do not spread / invade
other parts of the tissues / body, and
they are rarely a threat to life.
 Malignant tumors can invade
other organs, spread to distant
locations (metastasis) and become
life threatening.

7. Types of cancer
 cancers can be classified by the type of cell in which it
originates and by the location of the cell.
 .
cell Site / location cancer
Epithelial Digestive tract carcinoma
Blood cells WBC leukemia
lymphatic Lymph node lymphoma
Connective tissue bone sarcoma
melanocyte skin melanoma
Germ cells Testes/ovary Terratoma

8. Etiology of cancer
 Multifactorial in origin:
 Physical
 Chemical
 Biological (viruses )
 Environmental factors (physical & chemical agents)
 Hormonal
 Genetic
 Mutation

9. Physical agents
 X-ray
 Gamma ray
 UV ray

10. Chemicals
 Asbestos
 Aflatoxins: synthesised by the fungi “aspergillus flavus’
 Aniline (dye)
 Nitroso compounds
 Coloring agents
 Benzo (a) pyrene
 Polycyclic aromatic hydrocarbons (PAH)
 life style: tobacco chewing, smoking, alcohol

11. Initiation and Promotion in carcinogenesis
 Skin tumor in mice
 benzo(a)pyrene alone – no tumor
 benzo(a)pyrene followed by several applications of
croton oil – many tumors develop
 Application of croton oil alone – no tumors
 Initiation: benzo(a)pyrene –rapid and irreversible
modification of DNA
 Promotion: croton oil – slower process
 Most carcinogens cause initiation and promotion

12. Mutation
 Sudden change in the chemical structure of the DNA
- aberration in chemical structure
 The substance which causes mutation is known as
‘mutagen’
 Example:
 X-ray
 Gamma ray
 UV ray

13. Oncogenic virus
 Viruses which cause cancer are known as oncogenic virus
 They can integrate their gene into the host DNA and take
over the entire regulatory mechanism of the host cell. The
host cell will produce viral genome instead of host genome
(transformed cell).
 This leads uncontrolled multiplication of the host cells –
transformed cells.

14. Oncogenic virus..
SI No Virus cancer
1 Epstein-Barr virus
(EBV)
Nasopharyngeal
Burkitt’s lymphoma
2 Human Papilloma virus
(HPV)
Uterine Cervical
3 Hepatitis B virus
(HBV)
Hepatoma

15. Oncogenes
 Genes which can cause cancer are known as oncognes.
 Oncognes are present in normal cells also and in normal cells
they are known as proto-oncogenes
 We have more than 100 proto-oncogenes on various
chromosomes
 Example:
 ras gene (sarcoma virus)
 c-myc (avian myelocytoma virus)

16. Oncogenes..
 Products of these oncognes are involved in the
regulation of cell cycle
 These products may be growth regulating factor /
receptor
 These oncogens are under the control of regulator
genes and expressed only when required.
 Virus can carry these gene and transmit it to
individuals

17. Activation of Proto-oncogenes to
oncogenes
 Promoter Insertion
 Enhancer Insertion
 Chromosomal Translocations
 Chronic myeloid leukemia- Philadelphia chromosome
 Chromosome 9(abl) and 22 (bcr),Reciprocal translocations
 Burkitt’s lymphoma- Chromosome 8 (c-myc)and 14 (IgG)
 Gene Amplification
 Point mutation

18. Chronic Myeloid Leukemia
bcr-abl gene
product -
tyrosine kinase
activity

19. Anti-oncognes / onco-suppressor gene
 The genes which prevent cancer are known as anti-
oncogenes or onco-suppressor genes
 The products of these genes act as breaks and
regulate cell proliferation
 When these genes are deleted / mutated then it leads
cancer

20. Anti-oncogene /onco-suppressor gene
Anti-oncogene /
onco suppressor
gene
Cancer
(due to
mutation of the
gene)
p53 Breast cancer, colon
cancer
BRCA1 & BRCA2 Breast cancer
RB Retinoblastoma in
children
WT Wilms’ tumor

21. P53 tumor suppressor gene
 53kDA – nuclear phosphoprotein - unstable
 It can activate DNA repair proteins when
DNA has sustained damage.
 It can arrest growth by holding the cell cycle
at the G1/S regulation point on DNA damage
recognition
 It can initiate apoptosis
 P53  P21 G1/S arrest

22. The mammalian cell cycle
G1
S
G2
M
G0
DNA synthesis and
histone synthesis
Growth and
preparation for
cell division
Rapid growth and
preparation for
DNA synthesis
Quiescent cells
phase
phase
phase
phase
Mitosis

23. Cyclins in cell cycle progression
Cyclin Kinase Function
D CDK4,
CDK6
Progression past G1/S
boundary
E,A CDK2 Initiation of DNA synthesis in
early S phase
B CDK1 Progression from G2 to M

25. Telomerase and cancer
 Active in cancer cells and proliferating normal cells
 RNA primer at 5’end of newly synthesized strands
cannot be replaced with DNA
 Shortening of the ends of chromosomes at each
replication, with loss of important genes
 In humans telomeres consist of 1000 or more arrays
of TTAGGG repeats at the 3’ ends
 Genomic stability in germ-line cells is maintained by
Telomerase

26. Characteristics of cancer cells
1. uncontrolled proliferation
2. abnormal nucleus
3. loss of anchorage
4. disorganized multilayer (loss of contact inhibition)
5. forms tumor
6. undergoes metastasis & angiogenesis
7. lack of differentiation into specialized cells.
8. increased rate of anaerobic glycolysis

27. Cancer cells: Biochemical changes
 Increased synthesis of DNA & RNA
 Increased rate of aerobic and anaerobic glycolysis to
meet the increased demand for energy for more
cells.
 the rate of anaerobic glycolysis is tremendously
increased

28. Normal cell Cancer cell
Controlled cell proliferation Uncontrolled proliferation
Contact inhibition No Contact inhibition
Normal nucleus Abnormal nucleus
Organised , single layer Disorganised, multilayer
Differentiated cells Non differentiated cells
---- Metastasis & angiogenesis
apoptosis
Does not undergo apoptosis
telomerase activity stops
after about 50 cell cycles
Increased & persistent
telomerase activity

29. Standard cancer treatment
 Surgery:
removal of cancerous tissue
 Radiotherapy:
destruction of cancer cells using
radioactive rays
 Chemotherapy:
killing cancerous cells using drugs

30. Antimetabolites/Anticancer drugs
Anticancer drug chemistry Mechanism of action
methotrexate Folic acid analogue Inhibits
dihydrofolate reductase (THF)
6-mercaptopurine Purine analogue Inhibits formation of AMP
6-thioguanine Purine analogue Inhibits
thymidylate synthesis
Mitomycin C antibiotic Linking DNA base pairs
Actinomycin D antibiotic Inhibits transcription
cisplatin Platinum compound Forms DNA adducts
Vinblastine &
vincristine
alkaloids Inhibits spindle movement
(mitosis)

31. Cancer prevention: Antioxidants
 Prevents / scavenges free radicals.
 Can detoxify carcinogens
 Antioxidant vitamins:
 Vitamin A
 Vitamin E
 Vitamin C
 Vegetables & fruits

32. Tumor Markers

33. Ideal tumor marker
 Must be produced by tumor cells
 Should not be present in normal / healthy / benign
condition
 Must be detectable in body fluids
 It could be used for screening the presence of cancer
in asymptomatic patients.

34. Tumor marker:
Criteria for diagnostic marker
1. Highly specific
2. Highly sensitive
3. able to differentiate between neoplastic & non neoplastic
diseases
4. increase in level should precede neoplastic process

35. Tumor markers: uses
 Diagnosis
 Prognosis
 Localization
 Monitoring the treatment

36. Tumor marker: classification
 Tumor markers are classified into various groups:
 Enzymes
 Hormones
 Proteins
 Oncofoetal antigen
 Genes
 Carbohydrate antigen
 Blood group antigen
 Receptors

37. Oncofoetal antigens
 Oncofoetal antigens are proteins produced during
foetal life and present in high concentration during
foetal life and decreased to low concentration and
disappears after birth.
 This protein will reappear in cancer patients
 Alpha foetoprotein (AFP)
 Carcinoembryonic antigen (CEA)

38. Alpha foetoprotein (AFP)
 It’s molecular weight is 70000
 It is foetal albumin & resembles with adult albumin
 It’s normal level in adult: less than 10ug / L
 More than 300 ng / L is associated with cancer
 It’s level is Elevated in:
 Hepatocellular carcinoma
 Pregnancy with foetal abnormality (neural tube defect)
 Germ cell tumor
 Elevated level is also seen in:
 Hepatitis, cirrhosis & pregnancy.

39. Carcinoembryonic antigen (CEA)
 It consists of large family of cell surface glycoprotein.
 It’s molecular weight is ranging from 150 to 300 KD
 It is normally produced by the embryonic tissue of
liver, pancreas & gut.
 It level is elevated in:
 Colorectal cancer, Gastrointestinal cancer, Pancreatic
cancer
 Lung cancer, Breast cancer, Ovarian cancer, Uterine
cancer

40. Tumor marker: Enzymes
first group of tumor markers identified
ALP: primary / secondary involvement of liver cancer.
High level of ALP is also seen in secondary
involvement of bone cancer
Gamma glutamyl transferase (y-GGT) &
5’- Nucleotidase (5-NT) are also used to
diagnose liver cancer.
Prostatic Acid Phosphatase (PAP): it is elevated
in prostatic cancer.
Prostate specific antigen (PSA) is more
specific and sensitive than Acid
phosphatase

41. Tumor marker: Hormones
 Hormone is used as tumor marker in the following
conditions:
 High level of hormone is secreted by the endocrine
tissues where it is normally secreted.
 secreted by a non endocrine tissues where it is
normally not secreted - ectopic syndrome

42. Hormones as tumor marker
Hormone cancer site
ACTH
(pituitary)
lung ectopic
Calcitonin
(C cells of
thyroid)
Medullary thyroid ectopic
Parathyroid hormone
(parathyroid gland)
Breast, liver, lung,
etc.
ectopic
ADH
(posterior pituitary)
Adrenal cortex,
pancreatic &
duodenal
ectopic
Epinephrine
(adrenal medulla)
Pheochromocytoma normal

43. β Human Chorionic Gonadotropin
(β -hCG)
 It is synthesised by trophoblast of placenta
 It is a glycoprotein and its molecular weight is 45 KD
 It has two dissimilar subunits
 It’s alpha submit is identical with FSH, LH & TSH
 Beta subunit is specific for HCG
 Normal value is less than 20 IU / L
 It’s level is elevated in:
 trophoblastic tumour
 choriocarcinoma
 Germ cell tumor

44. Tumor marker: Protein
 Prostate specific antigen (PSA): it is useful in diagnosis
of prostate cancer
 Bence- Jones Proteins: plasma cell from B-lymphocyte
proliferates and produces light chain immunoglobulin known
as M-protein (paraprotein).
 It is used for diagnosis of multiple myeloma
 It has characteristic property towards heat treatment.
 It is precipitated at 50o
- 60o
C and re dissolves at 90o
C. On
cooling, it again precipitates

45. Carbohydrate antigen (CA 125)
 It is a glycoprotein & Mol wt : 10 million
 Normal level is less than 35 U / ml.
It is elevated in:
 Ovarian cancer
 Pancreatic cancer
 GI tract cancer

46. Tumor marker: gene
 Oncogenes can be used as tumor markers:
oncogene cancer
ras Sarcoma
c-myc Leukemia & lymphoma

47. Tumor marker: gene
 Antioncogenes as tumour markers:
Tumor suppressor gene cancer
p53 Breast cancer &
colon cancer
BRCA1 & BRCA2 Breast cancer
RB retinoblastoma

48. Receptors
 Estrogen & Progesterone receptors (ER & PR) are useful as
prognostic indicator and also to decide hormonal therapy in
breast cancer
 ER positive tumor tissue necessitate hormonal treatment for
effective treatment
 PR assay is a useful adjunct to ER assay for breast cancer.