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Prevention
Modalities of treatment
• Local therapy:
– -surgery
– -radiation therapy
• Systemic treatment:
– chemotherapy
– Hormonal therapy
– Monoclonal antibodies
– Radioactive material
• Supportive care
• Non-conventional therapy
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Surgery
• Surgery was the first modality used successfully in the
treatment of cancer.
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Surgery for prevention
• Patients with conditions that predispose them
to certain cancers or with genetic traits
associated with cancer can have normal life
span with prophylactic surgery.
-colectomy .
-oophorectomy.
-thyroidectomy.
-removal of premalignant skin lesion .
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Radiation therapy
Teletherapy
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• Telepathy often delivered in the form of photon beams
(either x-rays or gamma rays).
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Complications of radiation
• There are two types of toxicity:
– acute and long-term toxicity.
Radionuclides
• For decades have been used systemically to treat
malignant disorders.
• Phase non-specific:
– The drugs generally have a linear dose-response curve ( the drug
administration, in the fraction of cells killed).
• Phase specific:
– Above a certain dosage level, further increase in drug doesn’t result in
more cell killing, but one can alter duration of infusion.
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Chemotherapeutic agents:
• Alkylating agents
• Antimetabolites
• Antitumor antibiotics
• Plant alkaloids
• Other agents
• Hormonal agent
• Immunotherapy
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Alkylating Agents
Nitrogen
Ethylenimines Alkyl Sulfonates Nitrosoureas
Mustards
Legend
Drug Class
Sub-class
Prototype Drug
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Alkylating Agents
Mechanism of Action
Legend
Drug Class
Sub-class
Prototype Drug
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Folate
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Methotrexate
Mechanism of Action
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Pyrimidine Antagonists
• Fluorouracil - S-phase
• Cytarabine
• Gemcitabine
• Capecitabine
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MTX X
5-FU
X
Figure 2. This figure illustrates the effects of MTX and 5-FU on the
biochemical pathway for reduced folates.
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Mechanism of Action 5-FU
• 5-FU inhibits thymidylate synthase
therefore causing depletion of Thymidylate
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Therapeutic Uses of 5-FU
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Plant Alkaloids
Vinblastine
Vincristine Etoposide Topotecan Paclitaxel
Vinorelbine
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Vinca Alkaloids
Mechanism of Action
• Vinblastine
– Systemic Hodgkin’s disease
– Lymphomas
• Vincristine
– With prednisone for remission of Acute Leukemia
• Vinorelbine
– non-small cell lung cancer
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Taxanes
Mechanism of Action
• Mitotic “spindle poison” through the enhancement
of tubulin polymerization
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Taxanes
Therapeutic Uses
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Antibiotics
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Anthracyclines
Mechanism of Action
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Anthracyclines
Therapeutic Uses
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Hormonal Agents
Legend
Drug Class
Sub-class30
Prototype Drug
Anti-Estrogens
• Tamoxifen (SERMs)
• Raloxifene (SERMs)
• Faslodex
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Tamoxifen
• Selective estrogen receptor modulator (SERM), have both estrogenic
and antiestrogenic effects on various tissues
• Binds to estrogen receptors (ER) and induces conformational changes
in the receptor
• Most of tamoxifen’s affects occur in the G1 phase of the cell cycle
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Tamoxifen
Therapeutic Uses
O H
O H
Testosterone Dihydrotestosterone
(DHT)
• Leuprolide
• Goserelin
LHRH (Secreted LHRH-Agonist
by hypothalamus) Added
LHRH-Receptor
(On Pituitary Cell)
LH
(Secreted) Initially: Chronically:
Secreted Levels LHRH-Receptors
of LH Increase disappear, LH
(Flare) secretion decreases
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(Castrate)
Gonadotropoin-Releasing Hormone Agonist
Mechanism of Action
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Aminogluthethimide
Mechanism of Action
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Miscellaneous Anti-cancer Agents
• Asparaginase
• Hydroxurea
• Mitoxantrone
• Mitotane
• Retinoic Acid Derivatives
• Amifostine
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Asparaginase
• An enzyme isolated from bacteria
• Causes catabolic depletion of serum
asparagine to aspartic acid and ammonia
• Resulting in reduced blood glutamine levels and
inhibition of protein synthesis
• Neoplastic cells require external source of
asparagine
• Treats childhood acute leukemia
• Can cause anaphylactic shock
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Hydroxyurea
• An analog of urea
• Inhibits the enzyme ribonucleotide reductase
• Resulting in the depletion of deoxynucleoside
triphosphate pools
• Thereby inhibiting DNA synthesis
• S-phase specific agent
• Treats melanoma and chronic myelogenous
leukemia
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Mitoxantrone
• Structure resembles the anthracyclines
• Binds to DNA to produce strand breakage
• Inhibits DNA and RNA synthesis
• Treats pediatric and adult acute myelogenous
leukemia, non-Hodgkin’s lymphomas, and
breast cancer
• Causes cardiac toxicity
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Complication of Chemotherapy:
• Every chemotherapeutic will have some
deleterious side effect on normal tissue .
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Criteria used to describe response are
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Tumour Immunotherapy: questions
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How can we harness the immune response?
B Th
Th cells educate
other T/B cells
CTL CTL
APC recruits T cells
Broken up to able to recognise CTL recognise
release antigens tumour antigens and destroy other
T tumour cells
APC T
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‘Passive’ immunotherapy
MØ NK
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‘Active’ immunotherapies
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Effective
therapies
Complete regression of a
large liver metastasis from
kidney cancer in a patient
treated with IL-2.
Regression is ongoing
seven years later
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Other Immunostimulants
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Heat Shock Proteins for Therapy
ST
RE HSPs protect the delicate
SS functions of the cell.
ES
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Heat Shock Proteins
(HSP70)
NH4 COOH
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How is the anti-tumour effect produced?
NK
tumour
peptides
TAP system presented to
Transporter Associated with CTL / NK
Peptide processing cells via HLA
CD91 Class I
endocytosis
receptor
APC
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Using whole cells for immunization
CTL
CTL
CTL
CTL
CTL CTL
tumour
tumour tumour tumour
tumourtumour
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Allogeneic Transplant-
The Original Immunotherapy.
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Dendritic cell sources for therapy
Common
Myeloid
Haemopoietic
Progenitor
Stem Cell
Circulating
Myeloid DC
Monocyte
CD34+
Stem Cell Ex vivo
GM-CSF + IL-
4
Ex vivo Immature
GM-CSF + mdDC
Flt-3 + TNF
Maturation
factors Mature
mdDC
CD34+ DC
DC developed from
patient monocytes
Tumour-specific
immune responses
measured
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Radioimmunotherapy (RIT)
Benefits of RIT
1. Targeted therapy
2. less severe side effects than chemotherapy
3. Ability to directly target and kill the cancer cells
Conformal radiotherapy, 3D conformal radiotherapy (3DCRT)
3D-CRT immobilizes the patient in a bed of styrofoam that is customized for his
body. A computer generates a precise image of his internal organs.
The LINAC has a special device called a multileaf collimator that moves
around the patient and shapes the beams of radiotherapy to fit the
tumour.
Cancer Prevention and Early Detection
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Risk Factors
Age(>40)
Immunological factors:
Immunosuppressive drugs after transplantation
Immune disorder
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Biological factors
Viruses (e.g., Human Papilloma Virus-HPV, hepatitis B and C ) and
Bacteria (Helicobacter pylori)
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Screening/Early Detection
Techniques
• Breast Self Exam
• Breast Cancer • Mammograms
– Ages 40-49 every one to two
years
– 2nd leading cause of – Age 50 and over - yearly
cancer death in • Clinical Breast Exam
women • High risk women may
need to begin screening at
earlier ages
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Screening/Early Detection
Techniques
Colon/Rectum Cancer
Third most common cancer in both
men and women
• Beginning at Age 50:
• Stool blood test annually
• Digital rectal exam annually
• Sigmoidoscopy
• Colonoscopy (virtual)
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Lung Cancer
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Screening/Early Detection
Techniques
Prostate Cancer
• 2nd Leading cause of cancer death in men
• Beginning at Age 50
• DRE
• PSA
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Screening/Early Detection
Techniques
Ovarian Cancer
• Annual pelvic exam should be performed to
try and detect an ovarian mass.
• Pelvic ultrasound with vaginal probe may
become routine
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Screening/Early Detection Techniques
Cervical Cancer • Pelvic Exam
• Screening should begin • PAP Test
approx. 3 years after a
women begins to have
sexual intercourse, but
no later than 21 years
old.
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Other Screening Possibilities
• Tumor Markers
• EX: PSA – Prostate Cancer, CA-125 Ovarian Cancer
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Diagnostic Tests
• Physical Exam
– Examination of the entire body
– Lymph node bearing areas
– Abdomen is checked to detect enlargement of
any organs
– Exam of the pelvic area in women, including
PAP smear.
– Digital rectal exam for men and women
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Diagnostic Tests
• Lab Tests
– If cancer is present
blood tests can show
any effects of the
disease on the body.
– FOBT - fecal occult
blood test
– Urinalysis –
examination of the
urine
– CBC - complete blood
count
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Radio imaging and Cancer
Cancer imaging can be categorized into :
a. Anatomic: Anatomic images, primarily obtained using x-ray
computerized tomography (CT), magnetic resonance imaging (MRI),
or ultrasound (US), can be used for tumor detection and
determination of tumor size.
• The Fluc enzyme catalyzes adenosine triphosphate (ATP)–, Mg2+-, and O2-
dependent conversion of d-Luciferin to Oxyluciferin, emitting
bioluminescence. The Rluc and Gluc enzymes catalyze ATP-independent
oxidation of Coelenterazine, emitting light.
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