Presentation for Cancer from (Molecular Biology) point of view

1. Professor Dr. Mona Morsy
By/ Akram Ismail Abd El Rahman
/

2. CONTENTS
 Introduction
3
 Definition
5
 Basic molecular genetics
10
 Classification
12
 Causes and Risk factors
19
 Genetic nature of cancer
29
 Oncogenes
40
 Tumor and suppressor genes
50

3. INTRODUCTION
 Despite decades of intensive biomedical
research, cancer remains a significant
cause of morbidity and mortality
worldwide, account for more than 20% of
all deaths
 Cancer is a complex disease that result
from the same basic process of
uncontrolled growth: cells divide and
multiply as the body needs them. When
these cells continue multiplying when the
body doesn't need them, the result is a

4. INTRODUCTION
 A mass that invades neighbouring tissues
and may metastasize to more distant sites
 The growth is autonomous increasingly
malignant, if untreated ,invariably fatal
 Tumor formation is a multistep process
involving many of genetic changes in the
evolving tumor cell population
 These growths are considered either
benign or malignant, tumours are
classified by site, tissue type and degree
of malignancy
 Most cancer are disorders of later life, but
some affect childhood

5. CANCER
 Cancer is a genetic disorder in which
the normal control of cell growth is
lost. The basic mechanism in all cancer
is mutation, either in the germ line or
much more frequently, in somatic cells.
Cancer is multi-factorial diseases,
much remains to be learned about the
genetic processes of carcinogenesis
and about the environmental factors
that alter DNA and thus lead to
malignancy

6. CANCER
 What is Cancer?
 Uncontrolled growth and spread of abnormal
cells
 Neoplasms
 Malignant tumors
 Benign tumors
 Cellular Change/Mutation Theories
 Spontaneous errors
 External agents
 Oncogenes

7. CELLS GROW, REPLICATE
AND REPAIR BODY
ORGANS.
THE GENETIC
MATERIAL (DNA/RNA)
AND YOUR IMMUNE
SYSTEM REGULATE
THIS PROCESS.
 Cells represent the
smallest,
functional unit of
our existence
which contains
cytoplasm and a
nucleus (i.e.
metabolism,
reproduction, day
to day functions)
 Cells have a
specialized
function
depending on their
Healthy Cells

8. The division (mitosis) of normal cells is precisely controlled
Cancerous cells divide repeatedly out of control, they crowd out other
normal cells and function abnormally.
They can also destroy the correct functioning of major organs.

10. BASIC MOLECULAR GENETICS
 Somatic cell is any biological cell forming the
body of an organism
 Germ cells are cells that give rise to gametes
 Gametes : is a cell that fuses with another cell
during fertilization (conception)
in organisms that sexually reproduce, witch
carry half the genetic information of an
individual.
 Stem cells are cells that can divide through
mitosis and differentiate into diverse
specialized cell types.

11. DIFFERENT TYPES OF CELLS
 Blood cells
 Muscle cells
(smooth,
striated,
cardiac)
 Nerve cells
 Bone cells
 Cartilage cells
 Liver (hepa)

12. THE CELL CYCLE AND CANCER
 Neoplasm- abnormal growth of cells
 Benign neoplasms are not cancerous
Encapsulated; Do not invade
neighboring tissue or spread
 Malignant neoplasms are cancerous
Not encapsulated; Readily invade
neighboring tissues
May also detach and lodge in distant
places – metastasis

13. TUMORS
 Benign Tumors
(noncancerous)
 Enclosed in a
fibrous shell or
capsule.
 Take up space
 Concerned if they
interfere with
surrounding
tissues or vessels
or impede the
function of the
body.
• Malignant Tumors
(cancerous)
• Not usually
contained –
metastasis
• Invade and emit claw
like protrusions that
disrupt the RNA and
DNA of normal cells
(these cancerous cells
act like a virus).

14. CLASSIFICATION OF CANCER
 Cancers may be classified by their
primary site of origin or by their
histological or tissue types
 Classification by tissue types
 The international standard for the
classification and nomenclature of
histologies is the International
Classification of Diseases for Oncology

15.  Based on tissue types cancers may be classified
into six major categories:
 1. Carcinoma
Originates from the epithelial layer of cells that form
the lining of external parts of the body or the
internal linings of organs within the body.
Carcinomas, malignancies of epithelial tissue,
account for 80 to 90% of all cancer cases.
Carcinomas usually affect organs or glands capable
of secretion including breast, lungs, bladder, colon
and prostate.
Carcinomas are of two types – adenocarcinoma and
squamous cell carcinoma. Adenocarcinoma
develops in an organ or gland and squamous cell
carcinoma originates in squamous epithelium.
Adenocarcinomas may affect mucus membranes
and are first seen as a thickened plaque-like white
mucosa. These are rapidly spreading cancers.

16.  2. Sarcoma
Originate in connective and supportive
tissues including muscles, bones, cartilage
and fat. Bone cancer is one of the sarcomas
termed osteosarcoma. It affects the young
most commonly.
Other examples include chondrosarcoma (of
the cartilage), leiomyosarcoma (smooth
muscles)
 3. Myeloma
These originate in the plasma cells of bone
marrow. Plasma cells are capable of
producing various antibodies in response to

17.  4. Leukemia
 This a group of cancers that are grouped within blood
cancers. These cancers affect the bone marrow which is
the site for blood cell production. When cancerous, the
bone marrow begins to produce excessive immature
white blood cells that fail to perform their usual actions
and the patient is often prone to infection.
 Types of leukemia include:
 Acute myelocytic leukemia (AML) – these are
malignancy of the myeloid and granulocytic white blood
cell series seen in childhood.
 Chronic myelocytic leukemia (CML) – this is seen in
adulthood.
 Acute Lymphatic, lymphocytic, or lymphoblastic
leukemia (ALL) – these are malignancy of the lymphoid
and lymphocytic blood cell series seen in childhood and
young adults.
 Chronic Lymphatic, lymphocytic, or lymphoblastic
leukemia (CLL) – this is seen in the elderly.
 Polycythemia Vera or erythremia – this is cancer of

18.  5. Lymphoma
 These are cancers of the lymphatic system.
Unlike the leukemias, which affect the blood
and are called “liquid cancers”, lymphomas
are “solid cancers”. These may affect lymph
nodes at specific sites like stomach, brain,
intestines etc. These lymphomas are
referred to as extranodal lymphomas.
 Lymphomas may be of two types –
Hodgkin’s lymphoma and Non-Hodgkin’s
lymphomas. In Hodgkin lymphoma there is
characteristic presence of Reed-Sternberg
cells in the tissue samples which are not
present in Non-Hodgkin lymphoma.

19.  6. Mixed types
These have two or more components of
the cancer. Some of the examples
include mixed mesodermal tumor,
carcinosarcoma, adenosquamous
carcinoma and teratocarcinoma.
Blastomas are another type that
involves embryonic tissues.

20. CLASSIFICATION BY GRADE
Cancers can also be classified according to grade. The
abnormality of the cells with respect to surrounding
normal tissues determines the grade of the cancer.
Increasing abnormality increases the grade, from 1–4.
 Cells that are well differentiated closely resemble
normal specialized cells and belong to low grade
tumors. Cells that are undifferentiated are highly
abnormal with respect to surrounding tissues. These
are high grade tumors.
 Grade 1 – well differentiated cells with slight
abnormality
 Grade 2 – cells are moderately differentiated and
slightly more abnormal
 Grade 3 – cells are poorly differentiated and very
abnormal
 Grade 4 – cells are immature and primitive and
undifferentiated

21. CLASSIFICATION BY STAGE
 Cancers are also classified individually according to their stage.
There are several types of staging methods. The most
commonly used method uses classification in terms of tumor
size (T), the degree of regional spread or node involvement (N),
and distant metastasis (M). This is called the TNM staging.
 For example, T0 signifies no evidence of tumor, T 1 to 4 signifies
increasing tumor size and involvement and Tis signifies
carcinoma in situ or limited to surface cells. Similarly N0
signifies no nodal involvement and N 1 to 4 signifies increasing
degrees of lymph node involvement. Nx signifies that node
involvement cannot be assessed. Metastasis is further classified
into two – M0 signifies no evidence of distant spread while M1
signifies evidence of distant spread.
 Stages may be divided according to the TNM staging
classification. Stage 0 indicates cancer being in situ or limited to
surface cells while stage I indicates cancer being limited to the
tissue of origin. Stage II indicates limited local spread, Stage III
indicates extensive local and regional spread while stage IV is
advanced cancer with distant spread and metastasis.

22. CLASSIFICATION BY SITE OF ORIGIN
 By primary site of origin, cancers may be
of specific types like breast cancer, lung
cancer, prostate cancer, liver cancer renal
cell carcinoma (kidney cancer), oral
cancer, brain cancer etc.

24. CANCER RIBBON

26. HOW CAN NORMAL CELL BECOME CANCER CELL
?
1. Genetic instability
2. Autonomous growth
3. Insensitivity to internal and external
antiproliferative signals
4. Resistance to apoptosis and other forms of
induced cell suicide
5. Unlimited cell division potential
6. The ability to induce new blood vessel
formation , a process termed angiogenesis.
7. Locally invasive behavior, which uniquely
distinguishes malignant from benign
neoplasms.
8. Evasion of the immune system.

27. RISK FACTORS (MULTI-FACTORIAL)
 Exposure to Cancer-causing agents
 Cellular Mutations (what agents cause this?
Environment & Lifestyle agents)
 Genetics & Hormone exposure (i.e. breast
cancer)
 Occupation and Environment Factors
 Social and Psychological Factors
 Chemicals in Food
 Viral (i.e. herpes, HPV, mononucleosis) create an
opportunistic environment
 Medical Factors
 Risks for Cancer-Lifestyle
 Smoking among greatest
 Nutrition/exercise

28. FACTORS BELIEVED TO CONTRIBUTE TO GLOBAL
CAUSES OF CANCER

30. CAUSES OF CANCER
 Randomly acquired through errors in DNA
replication
 Inherited and thus present in all cells from
birth. The heritability of cancers are usually
affected by complex interactions between
carcinogens and the host genome
 Carcinogens such as tobacco smoke,
radiation, chemical or infectious agents

31. WHAT CAUSES CANCER
 Biological Factors
 Genetic predisposition
 Reproductive and hormonal risks
Hereditary predisposition – Some families
are more susceptible to getting certain cancers.
Remember you can’t inherit cancer its just that
you maybe more susceptible to getting it.

32. WHAT CAUSES CANCER
 Occupational and Environmental
Factors
 Asbestos, nickel, chromate
 Radioactive substances
Ionising radiation – X Rays, UV light
 Viral Factors
 Herpes-related virus and human
papillomavirus
 Chemicals in Food
 Sodium nitrate
 Clostridium botulism

33. WHAT CAUSES CANCER
 Social and Psychological Factors
 Stress
 Decrease negative emotions
There is connection between stress,
immune system and cancer, that is
changing the direction of research: it now
appears that cancer cells make proteins
that actually tell the immune system to let
them alone and even to help them grow.
cancer can weaken the immune system
and allowing tumor to grow

34. WHAT CAUSES CANCER
 Medical Factors
 Diethylstilbestrol (DES)
 Chemotherapy
 Any agent that causes cancer is called a
carcinogen and is described as
carcinogenic

36. GENETIC NATURE OF CANCER
 Nearly all cancers are caused by abnormalities
in the genetic material of the transformed cell
 In order for a normal cell to transform into a
cancer cell, genes regulate cell growth and
differentiation must be altered. When normal
regulation is altered, uncontrolled growth is
initiated
 Genetic changes can occur at many levels, from
gain or loss of entire chromosomes to a
mutation affecting a single DNA nucleotide
 New aspects of the genetics of cancer
pathogenesis, such as DNA methylation and

37.  Cancer is a genetic disorder in which the normal
control of cell growth is lost, the basic mechanism
in all cancer is mutation. Carcinogenic agents are
involved through causing mutation
 The mutation affects gene responsible for cell
proliferation, cell development and other cellular
activities
 Initiation of cancer; cells undergoing a series of
genetic mutation or alteration which result in their
instability to respond normally to
intracellular/extracellular signals that control
proliferation, differentiation and death

38.  Germline mutations are responsible for 5% of
cancer cases, this is also called familial cancer.
These mutations are present in every cell of the
body and are passed from parent to child
 Sporadic cancer or somatic mutation are
caused by tobacco, over-exposure to UV
radiation, and other toxins and chemicals.
These mutations are not in every cell of the body
and are not passed from parent to child

39. CHARACTERISTICS OF CANCER CELLS
 Lack differentiation (control)
 Have abnormal nuclei
 Form tumors
 Mitosis controlled by contact with
neighboring cells – contact inhibition
 Cancer cells have lost contact
inhibition

40. CANCER CELLS VERSUS NORMAL
CELLS

41.  Cancer arises from the mutation of a normal gene.
 A factor which brings about a mutation is called a
mutagen.
 It is thought that several mutations need to occur
to give rise to cancer
 Mutated genes that cause cancer
are called oncogenes.
 Any agent that causes cancer is called a
carcinogen and is described as carcinogenic.
 Cancerous cells do not self destruct and continue
to divide rapidly producing millions of new
cancerous cells.

48. ONCOGENES
 Oncogenes are known by three letter abbreviation
which reflect their origin or the type of tumor with
which they are associated
 Cancer-promoting oncogenes: if oncogene is
altered or over expressed, either as a result of
mutation in the gene itself or by altered external
control, the cell in which the change occurred can
undergo uncontrolled growth, eventually malignant.
Most oncogenes are mutated forms of normal genes ,
called proto-oncogenes
 Two oncogenes that have been found to be over
expressed in a variety of cancers include :
c-MYC (regulator gene that codes for a transcription
factor)

49.  Mutations in DNA can lead to changes in protein
function or expression that increase the potential
for cancer initiation, progression, or metastasis.
 Tumor suppressor genes regulate and control
cellular growth.
 Oncogenes promote cell growth.
 Types of Proto-oncogenes:
 Cellular oncogenes(c-oncogenes): proto-
oncogene which have been mutate in any
individual
 Normal oncogenes(n-oncogenes): proto-
oncogenes that have not been found to mutate

50. CHARACTERISTIC OF CELLULAR PROTO-ONCOGENE
These are typical cellular genes with typical
control sequences. As eukaryotic genes:
 Most have introns
 They are always at same place in genome
 No LTR sequences
They show normal Mendelian inheritance because
they are normal genes, essential to the function
of the cell
Cellular oncogenes are expressed by the cell at
some period of life of the cell, they are usually
proteins that are involved in growth control
Cellular oncogenes are highly conserved

51. ACTIVATION OF PROTO-ONCOGENES
 Point mutations
 Deletions, or insertions that leads to hyperactive
product
 Deletion, or insertions in the promoter region of a
proto-oncogene that lead to increased transcription
Gene amplification events leading to extra chromosomal
copies of proto-oncogene lead to normal protein
greatly overproduced. Amplified segment of DNA are
often detected as two types of cytogenetic change,
double minute and homogeneously staining regions
Chromosomal translocation
 Relocation of a proto-oncogene to a new
chromosomal site that leads to higher expression
 Fusion between a proto-oncogene and a second gene,
which produces a fusion protein with oncogenic

55. TYPES OF ONCOGENES
 Oncogene can be classified to their cellular
location and function of their encoded
oncoproteins in the signal transduction pathway:
 Growth factors
 Growth factor receptors
 GTP binding proteins
 Post receptor tyrosine kinase
 Cytoplasmic oncogenes
 Nuclear oncogenes
 Apoptotic oncogenes

58. TUMOR SUPPRESSOR GENES
 Tumor suppressor genes (antioncogene)
Normal genes regulate cellular growth and play a critical
role in the normal processes of the cell cycle.
 These genes are also important for DNA repair and
cell signaling ”tell cells when to die(apoptosis or
programmed cell death)”
 The product of tumor suppressor genes normally
block abnormal growth and malignant transformation
 The absence of tumor suppressor gene function may
lead to dysregulation of normal growth control and
malignancy
 In contrast of mutations in proto-oncogene, which are
dominant in their action, most mutation in tumor

59.  Many oncogenes and tumor suppressors
exert their effects by interfering with cell
cycle checkpoints and apoptotic pathways,
allowing cancer cells to divide continuously
and accumulate.
 Loss of the ability to respond appropriately
to damaged DNA is particularly dangerous,
because it fosters genetic instability, a key
attribute of cancer cells.
 Loss of DNA damage checkpoint controls
results in an increased mutation rate,
accelerating the mutation of cancer-
associate genes, thus contributing to
carcinogenesis and disease progression.

60. TUMOR SUPPRESSOR GENE
 Genes that control cell division some suppressor
genes help control cell growth and reproduction
e.g. retinoblastoma gene (RB1). Abnormalities of
the RB1 gene can lead to a type of eye
cancer(retinoblastoma) in infants as well as to
other cancers
 DNA repair genes these are genes that fix any
mistakes made when DNA is replicated. Mistakes
that aren’t fixed become mutations, which may
eventually lead to cancer e.g. Gene responsible for
‘hereditary nonpolyposis colon cancer’. When
genes don’t repair the errors in DNA, HNPCC can
result

63.  Inherited Abnormalities of some tumor
suppressor genes
Have been found in several cancers that tend to run in
families
 Mutations in p53, RB1, and the genes involved in HNPCC
 A defective APC gene causes familial polyposis a
condition in which people develop hundreds or thousands
of colon polyps, some of which may eventually may
acquire several sporadic mutations and turn into colon
cancer
 Abnormalities of the BRCA genes account for 5% to 10%
of breast cancer
 Non-inherited mutations of tumor suppressor
genes
 Acquired mutations of the p53 gene appear to be
involved in a wide range of cancers including lung,

66.  Loss of tumor suppressor gene function
can occur primarily by :
(1) homozygous deletion
(2) loss of one allele and mutational
inactivation of the second allele
(3) mutational events involving both alleles
(4) loss of one allele and inactivation of the
second allele by DNA methylation
 Proto-oncogenes can be converted to
oncogenes by :
(1) mutation of the proto-oncogene resulting in an
activated form of the gene
(2) gene amplification
(3) chromosomal rearrangement.

67. TELOMERE & TELOMERASE
 Telomeres contain stretches of terminal,
noncoding, repetitive DNA that cap the
ends of each chromosome, thereby
stabilizing them.
 Telomere DNA repeats are progressively
lost as cells divide and as a result of
oxidative DNA damage at the telomeres.

68.  Normal cells monitor their telomere
lengths and permanently exit the cell
cycle (cellular senescence) or commit
suicide (apoptosis) in response to
telomere shortening. This tumor-
suppressive telomere length
checkpoint involves TP53 and pRB.
 Loss of telomere length checkpoints
can lead to critical telomere shortening
that initiates chromosomal instability,
thus contributing to carcinogenesis.

69.  A majority of cancers and premalignant
lesions have abnormally short
telomeres.
 Most cancers express the enzyme
telomerase, which restabilizes the
telomeres and allows unlimited cell
division potential (“immortalization”),
thus telomerase represents an
attractive therapeutic target.

70. METASTASIS
 The process by which a tumor cell leaves the
primary tumor, travels to a distant site via the
circulatory system, and establishes a secondary
tumor
 Approximately 30% of newly diagnosed patients
with solid tumours present with metastases
Forms of cancer metastasis

71. PATHWAYS OF SPREAD
(1) Seeding of the body cavities and
surfaces
When a malignant neoplasm penetrates
into a natural ‘open field’ e.g. peritoneal
cavity
(2) Lymphatic Spread
Most common pathway for the initial
dissemination of carcinomas
Tends to follow the natural routes of
lymphatic drainage
(3) Haematogenous Spread
Typical of sarcomas
More readily via venous (than arterial)

72. 5 MAJOR STEPS IN METASTASIS
1. Invasion and infiltration of surrounding
normal host tissue with penetration of
small lymphatic or vascular channels;
2. Release of neoplastic cells, either or
single cells or small clumps, into the
circulation;
3. Survival in the circulation;
4. Arrest in the capillary beds of distant
organs;
5. Penetration of the lymphatic or blood
vessel walls followed by growth of the

74. ANGIOGENESIS
The formation of new blood vessels out of pre-
existing capillaries.
INVOLVES : Sprouting
Splitting
Remodeling of the existing vessels
Small localized
tumor
Angiogenesis
Tumor that can grow and spread

75. CELLULAR MECHANISMS OF TUMOUR
ANGIOGENESIS
(1) host vascular network
expands by budding of
endothelial sprouts or
formation of bridges
(angiogenesis);
(2) tumour vessels remodel
and expand by the
insertion of interstitial
tissue columns into the
lumen of pre-existing
vessels
(intussusceptions); and
(3) endothelial cell
precursors (angioblasts)
home from the bone
marrow or peripheral
blood into tumours and
contribute to the
endothelial lining of
tumour vessels
(vasculogenesis)
(4) Lymphatic vessels
around tumours drain the
interstitial fluid and
provide a gateway for

76. ACTIVATORS OF ANGIOGENESIS INHIBITORS OF ANGIOGENESIS

78. CANCER TREATMENT
 Chemotherapy treatment
 uses medicine to weaken and destroy
cancer cells in the body, including cells at
the original cancer site and any cancer
cells that may have spread to another part
of the body.
 Chemotherapy treatment
or "chemo," is a systemic therapy, which
means it affects the whole body by going
through the bloodstream.
 In some cases, chemotherapy is given

79. CANCER TREATMENT
 Radiation therapy (also called
radiotherapy)
 high-energy rays are used to damage
cancer cells and stop them from growing
and dividing.
 Radiation therapy is a local treatment; it
affects cancer cells only in the treated
area. Radiation can come from a machine
(external radiation).
 It can also come from an implant (a small
container of radioactive material) placed
directly into or near the tumor (internal
radiation). Some patients receive both

81. CANCER PREVENTION

82. CANCER PREVENTION
 Healthy lifestyle
 Exercise and proper breathing
 Balanced diet
 Complete rest and sleep
 Water (8 to 10 glasses daily)
 Eating Fruit on an empty stomach

85. FACING CANCER
 Detecting Cancer
 Magnetic Resonance Imaging (MRI)
 Computerized Axial Tomography scanning
(CAT scan)
 Prostatic ultrasound (rectal probe)
 Self-exam and check-ups

86. FACING CANCER
 New Hope in Cancer Treatments
 Surgery to remove tumor
 Chemotherapy
 Researching genes and cell mutations
 Talking with Your Doctor about Cancer
 Ask questions about type, treatment,
clinical trials
 Ask about surgery
 Ask why one treatment is preferred
 Get all your options