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.
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
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
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.
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
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
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
24.
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
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
35.
36.
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.
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
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
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
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
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
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
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
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
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
Immunocompromised individuals are at higher risk for cancer development
TS: cannot find tumor
NX: regional lymph nodes unable to be assessed
Rapidly dividing cells are more susceptible to radiation damage because there’s less time to repair DNA mutations. Daughter cells inherit mutated DNA. The downside is that radiation isn’t limited to targeting cancer cells, but also normal cells.
Limiting! Ex. Only targets cancer cells in M-phase (only a 1 hour window) multiple drugs used at once
A premenopausal woman might receive androgens with chemo whereas a postmenopausal woman may receive estrogen.