Dr. Ali K. Shaaeli MBChB, FACS 2016

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Dr. Ali K. Shaaeli
MBChB, FACS
2016
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To understand the biological nature of cancer
To understand the principles of cancer
prevention and early detection
To know the principles of cancer etiology and
the major causative factors
To know The likely shape of future
developments in cancer management
To know The multidisciplinary management
of cancer
To know The principles of palliative care
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The name ‘cancer’ comes from the Greek and
Latin words for a crab, and refers to the clawlike blood vessels extending over the surface
of an advanced breast cancer.
Cancer cells are psychopaths. They have no
respect for the rights of other cells. Their
proliferation is uncontrolled; their ability to
spread is unbounded. Their inexorable,
relentless progress destroys first the tissue
and then the person.
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Establish an autonomous lineage: a- resist signals
that inhibit growth. b- acquire independence from
signals stimulating growth
Obtain immortality
Evade apoptosis
Acquire angiogenic competence
Acquire the ability to invade
Acquire the ability to disseminate and implant
Evade detection/elimination
Genomic instability
Jettison excess baggage
Subvert communication to and from the
environment
Develop ability to change energy metabolism
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This involves developing independence from
the normal signals that control supply and
demand.
Cancer cells escape from this normal system
of checks and balances: they grow and
proliferate in the absence of external stimuli
regardless of signals telling them not to do
so.
Oncogenes, an aberrant form of normal
cellular genes, are a key factor in this process
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According to the Hayflick hypothesis, normal
cells are permitted to undergo only a finite
number of divisions. For humans, this
number is between 40 and 60.
Cancer cells can use the enzyme telomerase
to rebuild the telomere at each cell division,
so there is no telomeric shortening and the
lineage will never die out. The cancer cell has
achieved immortality.
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Apoptosis is a form of programmed cell death
which occurs as the direct result of internal
cellular events instructing the cell to die
Cells that find themselves in the wrong place
normally die by apoptosis
Cancer cells will be able to avoid apoptosis,
which means that the wrong cells can be in
the wrong places at the wrong times.
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A mass of tumor cells cannot, in the absence
of a blood supply, grow beyond a diameter of
about 1 mm.
The ability of a tumor to form blood vessels
is termed ‘angiogenic competence’ and is a
key feature of malignant transformation.
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Cancer cells have no respect for the structure
of normal tissues. They acquire the ability to
breach the basement membrane and thus
gain direct access to blood and lymph vessels
Three mechanisms to facilitate invasion:
(1) They cause a rise in the interstitial
pressure within a tissue;
(2) They secrete enzymes that dissolve
extracellular matrix; and
(3) They acquire motility.
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Once cancer cells gain access to vascular and
lymphovascular spaces, they have acquired
the potential to use the body’s natural
transport mechanisms
. They also need to acquire the ability to
implant.
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Cancer cells are simultaneously both ‘self’ and ‘not
self’.
(‘self’), they are, in terms of their genetic make up,
behavior and characteristics,
Foreign (‘not self’). As such, they ought to provoke an
immune response and be eliminated and it is entirely
possible that malignant transformation is a more
frequent event than the emergence of clinical cancer.
The possible role of the immune system in
eliminating nascent cancers Cancer cells, or at least
those that give rise to clinical disease, appear to gain
the ability to escape detection by the immune system.
This may be by suppressing the expression of tumorassociated antigens,
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A cancer Cells are dividing without proper checks
and balances.
Mutations, particularly those in tumor suppressor
genes, may have the ability to encourage the
development and persistence of further
mutations.
This gives rise to the phenomenon of genomic
instability – as it evolves, a cancer contains an
increasing variety and number of genetic
aberrations:
the greater the number of such abnormalities,
the greater the chance of increasingly deviant
behavior
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Cancer cells are geared to excessive proliferation.
They do not need to develop or retain those
specialized functions that make them good
cellular citizens.
They can therefore afford to repress or
permanently lose those genes that control such
functions.
This may bring some short-term advantages.
The longer-term disadvantage is that what is
today superfluous may, tomorrow, be essential.
This can leave cancer cells vulnerable to external
stress and may, in part, explain why some cancer
treatments work.
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Providing false information is a classic military
strategy.
Degrading the command and control systems of
the enemy is an essential component of modern
warfare. Cancer cells almost certainly use similar
tactics in their battle for control over their host.
Given the complexity of communication between
and within cells, this is not an easy statement to
prove or disprove. Nor does it offer any easy
targets for therapeutic manipulation.
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Blood flow in tumors is often sporadic and
unreliable. As a result, cancer cells may have
to spend prolonged periods starved of
oxygen – in a state of relative hypoxia.
Compared to the corresponding normal cells,
some cancer cells may be better able to
survive in hypoxic conditions.
This ability may enable tumors to grow and
develop despite poor blood supply.
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Cancer cells can alter their metabolism even
when oxygen is abundant, they break down
glucose but do not, as normal cells would do,
send the resulting pyruvate to the mitochondria
for conversion, in an oxygen-dependent process,
to carbon dioxide. This is the phenomenon of
aerobic glycolysis, and leads to the production of
lactate.
In an act of symbiosis, lactate-producing cancer
cells may provide lactate for adjacent cancer cells
which are then able to use it, via the citric acid
cycle, for energy production.
This cooperation is similar to that which occurs
in skeletal muscle during exercise.
The interplay between nature and nurture
Both inheritance and environment are important
determinants of cancer development. Although
environmental factors have been implicated in more
than 80 per cent of cases, this still leaves plenty of
scope for the role of genetic inheritance: not just
the 20 per cent of tumors for which there is no
clear environmental contribution but also, as
environment alone can rarely cause cancer, the
genetic contribution to the 80 per cent of tumors to
which environmental factors contribute.
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Syndrome
Gene
Inh Associated Tumors
MEN type
2b
RET
D
Familial
breast
cancer
BRCA1, BRCA2 D
Xeroderma Deficient
R
pigmentos nucleotide
um
excision repair
(XPA, B, C)
Medullary carcinoma of the thyroid
Phaeochromocytoma
Mucosal neuromas
Ganglioneuromas of the gut
Breast cancer
Ovarian cancer
Papillary serous carcinoma of the
peritoneum
Prostate cancer
Skin sensitive to sunlight; early onset
of cutaneous carcinomas (SCCs,
BCCs)
Environmental/behavioral factor
Associated tumors
Tobacco
Lung cancer
Head and neck cancer
Alcohol
Head and neck cancer
Oesophageal cancer
Hepatoma
UV exposure
Melanoma
Non-melanoma skin cancer
Fungal and plant
toxins
Obesity/lack
of physical exercise
Aflatoxins
Hepatoma
Breast
Endometrium
Kidney
Colon
Oesophagus
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Management is more than treatment
The traditional approach to cancer
concentrates on diagnosis and active
treatment. This is a very limited view that, in terms of
the public health, may not have served society well.
Cancer management can be considered as
taking place along two axes:
1-One an axis of scale, from the individual to
the world population;
2-The other based prevention to rehabilitation
or palliative care
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In 1998, Sir Richard Doll estimated that
30 per cent of cancer deaths were due to
tobacco use and that up
to 50 per cent of cancer deaths were related
to diet.
Screening involves the detection of disease in
an asymptomatic population in order to
improve outcomes by early diagnosis.
 a successful screening program must achieve
early diagnosis, and that the disease in
question has a better outcome when treated at
an early stage.
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Accurate diagnosis is the key to the
successful management of Cancer.
Precise diagnosis is crucial to the choice of
correct therapy
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It is not sufficient simply to know what a
cancer is;
it is imperative to know its site and extent.
Staging is the process whereby the extent of
disease is mapped out
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As the management of cancer becomes more
complex,
It becomes impossible for any individual
clinician to have the intellectual and technical
competence that is necessary to manage all
the patients presenting with a particular type
of tumors
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Diagnosis and staging
Removal of primary disease
Removal of metastatic disease
Palliation
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Within a month of their discovery in 1895,
x-rays were being used to treat cancer
it was assumed that the biological effects of
radiation resulted from radiation induced
damage to the DNA of dividing cells.
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Selective toxicity is the fundamental principle
underlying the use of chemotherapy in
clinical practice.
The importance of the principle is further
emphasized by the fact that, by itself,
chemotherapy is rarely sufficient to cure
cancer
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