This document provides an overview of cancer, including its causes, characteristics, diagnosis, and treatment. It discusses how cancer arises from uncontrolled cell growth due to genetic mutations and describes the hallmarks of cancer cells, such as evading apoptosis and sustaining proliferative signaling. The stages of cancer progression from initiation to promotion to metastasis are explained. Risk factors for cancer and methods for prevention, screening, and classifying tumors are also outlined. Finally, major treatment options are summarized, including surgery, radiation therapy, chemotherapy, hormonal therapy, biotherapy, and targeted therapy.

1. AN OVERVIEW OF CANCER
BY.DR REENA SINGH

2. Cells are born,
live for a given period of time
and then die
Bowen, 1998

3. Integrated balance between positive survival
factors and negative death signals decides
fate of cell
To die or not to die?

4. Uncontrolled growth of cells
Insufficient apoptosis

5. Phases of normal cell cycle
• G1 phase – post mitotic phase. Relatively
dormant - some RNA & protein synthesis
• S phase - DNA synthesis occurs
• G 2 phase – pre mitotic phase. Some RNA &
protein synthesis
• M Phase - cell division occurs
• G o Phase - resting phase

6. Cell Cycle

7. Cell proliferation
Cells divide and reproduce
Regulated so number of cells dividing = to
number dying or being shed
Cell types fit into 3 large groups:
Well differentiated neurons, skeletal and cardiac
muscle cells
Parent or progenitor cells
Undifferentiated stem cells

8. Cell differentiation
Cells transformed into different and more
specialized cell types
Adult cell achieves specific set of structural,
functional, and life expectancy characteristics
Orderly process

9. Normal Cellular Differentiation

10. Neoplasm - (new growth) abnormal mass of
tissue, the growth of which exceeds and is
uncoordinated with the normal tissues
Tumor - a non-specific term meaning lump or
swelling. Often syn. for neoplasm
Cancer - malignant neoplasm or tumor
Metastasis - discontinuous spread
of a malignant neoplasm
to distant sites

11. Cancer is a disorder of cellular
homeostasis disease in which
there is uncontrolled cell
division caused by:
• by mutation
• or by some other abnormal
activation of cellular genes that
control cell growth and cell
mitosis.
CANCER

12. • Cancer can kill the patient by:
• Local effects
• Systemic effects
• Why Do Cancer Cells Kill?
• Cancer tissue competes with normal tissues for nutrients.
• Because cancer cells continue to proliferate indefinitely, cancer cells
soon demand essentially all the nutrition available to the body or to
an essential part of the body.
• As a result, normal tissues gradually suffer nutritive death.

13. HALLMARKS OF CANCER

14. Cancer cell characteristics
• Cells fail to undergo normal cell proliferation and
differentiation
• Anaplasia – term used to describe lack of cell differentiation in
cancerous tissue
• Cancer cells do not function properly and do not die according
to time frame of normal cells

15. 1920s German Biochemist OTTO WARBURG –Biochemistry of
cancer cells
Cancer cells takeup large amounts of glucose,metabolize it to
lactic acid even in the presence of oxygen(WARBURG
EFFECT)
High rate of aerobic glycolysis under investigations

16. • Defect in respiratory chain ,tumor cells compensate ATP via
more glycolysis.
• Cancer cells ,less mitochondria
• Mitochondrial bound isoenzyme of hexokinase(HK-2),not
subjected to feedback control,increased uptake of glucose
• Mutations of isocitrate dehydrogenase detected in gliomas
and AML

17. Tumor growth
Rate of tissue growth in normal and cancerous
cells depends on:
Number of cells actively dividing or moving
through cell cycle
Duration of cell cycle
Number of cells being lost compared with number
of cells being produced

19. Characteristics of Benign and
Malignant Neoplasms

20. Benign Neoplasms
Well differentiated cells that cluster together
in single mass
Resemble cells of tissue of origin
Slow, progressive rate of growth
Expands, but unable to metastasize
Usually enclosed in fibrous capsule

21. Malignant Neoplasms
Less well differentiated cells
Able to break loose, enter circulation or lymph
system, and form secondary malignant tumors
at other sites
Grow rapidly, spread widely
Potential to kill regardless of original location

22. Benign vs. Malignant

23. Invasion and metastasis
Cancer spreads by:
Direct invasion and extension
Seeding of cancer cells in body cavities
Metastatic spread through blood or lymph
pathways

25. Metastasis :molecular level
• Epithelial-mesenchymal cell transition allows increases
movement of cells
• Changes in cell surface molecules involved(CAM)
• Increased proteinase activity (MP-2,MP-9)
• Existence of metastasis enhancer and suppressor genes
• Metastasis gene signatures may be detected by gene
microarray analysis

26. Process of metastasis

27. Sites of bloodborne metastases

28. Metastasis to
the liver
Metastasis to
the lungs

29. Metastasis to the brain

30. Metastasis to the bone

31. Cancer incidence and prevalence by
site and sex
Men
 Prostate
 Lung/Bronchus
 Colon/Rectum
 Urinary Tract
 Melanoma
Women
 Breast
 Lung /Bronchus
 Colon/Rectum
 Uterus
 Ovary

32. Estimated mortality
Men
• Lung/Bronchus
• Prostate
• Colon/rectum
• Pancreas
• Non-Hodgkin’s
lymphoma
Women
 Lung/Bronchus
 Breast
 Colon/rectum
 Pancreas
 Ovary

33. Carcinogenesis and major
risk factors
Terms important in carcinogenesis
 Two mutational routes that result in
uncontrolled cell proliferation are
characteristic of cancer:
 stimulation of gene causing hyperactivity
 inhibition of gene causing inactivity

34. a. Oncogene
• Cancer causing gene – altered gene
• Gene that promotes autonomous cell growth
in cancer cells
• Mutations of normal growth-regulating genes
Oncogenesis: mechanism by which normal cells mutate into cancer cells
Only one single altered gene copy can cause an overgrowth

37. • A proto-oncogene is a normal gene that can become an
oncogene due to mutations or increased expression. The
resultant protein may be termed an oncoprotein.
• Proto-oncogenes code for proteins that help to regulate cell
growth and differentiation.
• Proto-oncogenes are often involved in signal transduction and
execution of mitogenicsignals, usually through
their protein products. Upon activation, a proto-oncogene (or
its product) becomes a tumor-inducing agent, an oncogene.

38. Proto--oncogenes
Growth factors
Receptor tyrosine kinases
Membrane associated non receptor tyrosine kinases
G-protein coupled receptors
Membrane associated G-protein
Serine/threonine kinases
Nuclear DNA –binding/transcription factors

41. RAS
• Family of oncogenes encoding small GTPases
• Initially identified as transforming genes of
certain murine sarcoma viruses
• K-RAS,H-RAS,N-RAS
• Persistent activation due to mutation leads to
variety of cancers

42. MYC
Encodes a DNA –binding factor that can alter
transcription
Involved in cell growth,cell cycle progression,DNA
replication
Mutated in variety of tumors

43. Anti-oncogene/Suppressor gene
• Gene that inhibits proliferation of cells
• Genetic signal that normally inhibits
proliferation is removed – causes unregulated
growth
• “Turns off” or regulates unneeded cellular
proliferation

44. RB
• Tumor suppresor gene encoding the RB
protein
• RB regulates the cell cycle by binding to
elongation factor EF2
• Represses transcription of various genes
involved in the S phase of the cycle
• Mutation causes retinoblastoma ,certain other
tumors

45. P53
• Tumor suppresor gene that responds to
various cellular stresses.
• Induces cell cycle
arrest,apoptosis,senescence,DNA repair
• “the guardian of the genome”
• Mutated in 50 % of human tumors

46. oncogene
• Mutation in 1 or 2 alleles
sufficient
• Gain of function of protein
that signals cell division
• Mutation arises in somatic
cells,not inherited
• Some tissue preference
Tumor suppresor gene
• Both alleles must be
affected
• Loss of function of a protein
• Mutation present in germ
cell(can be inherited),or in
somatic cell
• Often strong tissue
preference(eg.RB –retina)

47. Cancer cell transformation
a. Initiation – 1st Step
• Exposure of cells to appropriate doses of
carcinogenic agent - makes them susceptible
to malignant transformation
• Irreversible alteration in cell’s genetic
structure
• Not usually significant to cells until 2nd step of
carcinogenesis

48. Cancer cell transformation
b. Promotion – 2nd step
•Unregulated accelerated growth in already
initiated cells by various chemical and growth
factors
•Characterized by reversible proliferation of
altered cell if promoter substance removed

49. Cancer cell transformation
c. Progression – 3rd step
•Cellular changes formed during initiation and
promotion assume increased malignant
behavior
•Cells divide in uncoordinated fashion, invade
and destroy neighboring tissue

50. Initiation, Promotion and Progression

51. Carcinogens and risk factors

52. Risk factors
1. Heredity
 Predisposition to approx. 50 types of cancer
has been observed in families
 10% of cancers have strong genetic link

53. 2. Hormones
• Thought to drive cell division
• Women – breast, ovary, endometrium
• Men – prostate, testis

54. 3. Immunologic mechanisms
Cancer associated with impairment or decline
in immune system. increase in:
People with immunodeficiency disease
Organ transplant pts taking immunosuppressant
drugs
Elderly

55. 4. Chemical carcinogens
Cigarette smoke
Workplace carcinogens
Air pollution
Diet
Alcohol

56. 5. Radiation
Ultraviolet exposure
Ionizing radiation exposure
Electromagnetic field exposure

57. 6. Oncogenic viruses
Incorporate themselves into genetic structure
of cell
Alter future generations of cell
Human papillomavirus (HPV)
Epstein-Barr virus (EBV)

58. Immunological defense against CA
Immune surveillance mechanisms
Cytoxic T cells - kill tumor cells
Natural Killer cells - directly lyse tumor cells
Monocytes/Macrophages - important in
detection of CA cells. Secret cytokines
B cells – produce antibodies that bind to and
kill tumor cells

59. Macrophage functioning in response to
malignant target cells

60. How cancerous cells evade
immune system
Depends on ability of immune system to
recognize cancer cells as being different from
self cells
Closely resemble cells they originate from
Process where cancer cells evade immune
system is called immunologic escape

61. Tumor associated antigens on surface of
malignant cells

62. Blocking Antibodies Preventing T-Cell from
Destroying Malignant Cell

63. Prevention and early
detection of cancer

64. Primary Prevention
Secondary Prevention
Tertiary Prevention

65. Preventive measures
Important role of health professionals
Must have knowledge and skills to educate
community about:
 health-related behaviors
 risk factors
screening and detection methods

66. 1. Patient education
Numerous factors influence degree of
knowledge people have about CA risk factors
and health promoting behaviors:
race
cultural influences
level of education
income
age

67. Seven Warning Signs of Cancer

68. B. Screening procedures for
different types of cancer sites
SBE for breast cancer
Rectal exams for prostate cancer
Sigmoidoscopy/colonoscopy
Occult blood for colon cancer

69. Ways of classifying cancer
Tumors are classified on basis of:
cell type
tissue of origin
benign or malignant
degree of differentiation
anatomic site
function

70. A. By anatomic site
Epithelial tissue - carcinomas
Connective tissue - sarcomas
Lymphatic tissue - lymphomas
Glial cells of the CNS - gliomas
Blood forming organs (mainly bone marrow)-
leukemias

71. B. Histological Analysis
(“Grading”)
Grade I: cells differ slightly from normal cells and
are well differentiated
Grade II: cells are more abnormal and moderately
differentiated
Grade III: cells are very abnormal (severe
hyperplasia) and poorly differentiated
Grade IV: cells are immature and primitive and
undifferentiated, no resemblance to tissue of
origin

72. C. Extent of disease (“Staging”)
Describes location and pattern of spread of tumor
TNM most common:
Tumor (primary)
Node
Metastasis

73. Clinical Staging
0 - CA in situ
I - tumor limited to tissue or organ
II - limited local spread
III - extensive local and regional spread
IV - metastasis

74. TREATMENT OPTIONS FOR CANCER

75. Major treatment options in
cancer treatment
Goals - Cure, Control, Palliation
Used to be considered cured if no cancer
recurrence for 5 years after treatment
Widespread invasions associated with poor
prognosis
Choice of Rx depends on staging - more
metastasis = more aggressive approach

76. Surgery
Approx 90% treated surgically
Main benefit - removal of tumor with minimal
damage to other body cells
Surgery involves risk
Usually followed by radiation or
chemotherapy

77. Radiation
Used to interrupt cellular growth. Can:
immediately kill cells
delay or halt cell cycle progression
cause damage in nucleus that causes cell
death after replication

78. Types of Radiation
1. External radiation - source placed outside the body
“Lethal tumor dose”: will eradicate 95% of tumor while preserving
normal tissue
2. Internal radiation/Brachytherapy - source placed
close to or directly in the tumor site
Seeds, beads, needle, catheter, etc.
Brachytherapy: limits radiation to duration of treatment?
Time, Distance, Shielding

79. Linear accelerator treatment for head and
neck cancer

80. Wet
desquamation
from RT
Dry desquamation
from RT

81. Chemotherapy
Systemic administration of anticancer
chemicals
Most agents are cytotoxic - interfere with
some aspect of cell division
More rapidly dividing cells more susceptible
Normal cells die too

82. Classifications
a. Cell cycle specific
Destroys cells in specific phases of cell cycle
b. Cell cycle non-specific
Act independently of cell cycle phases
Often combine with cell-cycle specific to
increase number of cells killed

83. ANTICANCER AGENTS
• Inhibitors of signal
transduction
• Monoclonal antibodies
• Anti-angiogenesis agent
• Anti-hormonal agents
• Affect diffrentiation
• IMATINIB
• TRASTUZUMAB
• BEVACIZUMAB
• TAMOXIFEN
• All –trans RETINOIC
ACID

84. Action Sites of CCS [Antineoplastic] Drugs

85. Hormonal therapy
Used for cancers that are responsive to or
dependent on hormones for growth:
breast
prostate
adrenal glands
endometrium

86. Biotherapy
• Active Immunotherapy – acts as nonspecific
stimulant of immune system
• Passive Immunotherapy – transfer of cultured
immune cells into person with cancer
– Sensitized NK cell
– T lymphocytes
– Cytokines

87. Biologic Response Modifiers
• Changes person’s biologic response to cancer
– Cytokines: IFNs, ILs that bind
– Monoclonal antibodies: produced by B-cells
– Hematopoietic growth factors

88. Targeted therapy
Drugs that target processes of cancer cells
specifically
Leave normal cells unharmed

89. Bone marrow and peripheral
blood stem cell transplantation
High dose chemo and radiation therapy used
to ablate or suppress bone marrow
Self or donor stem cells transplanted

90. Stem cell transplant

91. THANK YOU