Transcript What is Cancer

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 What is Cancer ?
Cancer is a disorder of cell division (leading cause of
death).
 Cancers most commonly occur in:
breast (♀) - prostate (♂) - lung - colon - rectum
 Common characteristics of neoplastic cells:
- Persistent proliferation and Immortality
-Dedifferentiation.
- Invasive growth
- Formation of metastasis
-Sustained angiogenesis.
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 Cancer Etiology
-The abnormal behavior of cancer cells results
from DNA alterations.
Malignant transformation results from a
combination of activation of oncogenes and
inactivation of tumor suppressor genes.
- These genetic alterations are caused by:
Chemical carcinogens (cigarette smoking).
Pathogens (hepatitis C virus, H. pylori).
Radiation (X-rays).
Hereditary factors.
Drugs (estrogen).
Pathophysiology of cancer
Chemicals,
viruses,
radiation,etc.
Acquired
mutations
Altered gene
expression
Proto-oncogenes to
oncogenes.
(Uncontrolled cell proliferation
and dedifferentiation)
Inherited
mutations
Inactivation of tumor
suppressor genes.
(Decrease apoptosis)
Development of
primary tumor
Invasiveness
Angiogenesis
Metastasis
Malignant transformation occur in three major stages:
1- initiation: DNA damage
2- promotion : multiplication
3- progression : growth and invasion
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Tumor staging
Most commonly applied staging system for solid tumors is
TNM (tumor-nodes-metastasis) classification where a numerical
value is assigned to each letter to indicate size or disease extent.
TNM system
T: refers to the size of the primary tumor (0-4)
e.g. T4 (large size tumor).
N: refers to the extent of lymph nodes involvement (0-4)
e.g. N0 (no lymph node disease).
Nx(Lymph nodes not assessed).
M: refers to the presence or absence of distant metastasis (0-1)
e.g. M1 (distant metastasis).
M0 ( No distant metastasis).
Mx (distant metastasis not assessed).
T2N1M0 (moderate size tumor with limited nodal disease and
no distant metastases).
Cancer Grading:
Tumor grade is the description of a tumor based on how
abnormal the tumor cells and the tumor tissue look under a
microscope.
Gx: Grade cannot be assessed (undetermined grade)
G1: Well differentiated (low grade)
G2: Moderately differentiated (intermediate grade)
G3: Poorly differentiated.
G4: undifferentiated (high grade)
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G1 = 40%
S = 39%
G2 = 19%
M = 2%
Checkpoints:
P27: G1-S
P53: G2-M
Growth Fraction = GF = Proliferating cells (S or M phase)
/resting cells (G0).
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 Treatment Modalities:
1.Surgery (solid tumors).
2. Radiation (solid tumors).
3. Drug therapy:
-Disseminated
cancers
(leukemias,
lymphomas & widespread metastases.
-Some localized tumors e.g. testicular
carcinoma.
-Adjuvant to surgery & radiation.
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 Goals of therapy:
- Cure e.g. Hodgkin̕ s disease
- Prophylaxis of recurrence
- Prolong survival
- Palliation of symptoms
Outcome of therapy depends on:
-General health of patient
-Responsiveness of cancer type (size, location,
grade, etc.).
-Drug resistance.
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Drug Selection
 Combination therapy is more effective than single drug
therapy
- Maximal cell kill
- ↓ Injury to normal cells.
- Slow/prevent development of drug resistant
Criteria of drug selection for combination therapy
- Different MOAs (act at diff. cell-cycle stages)
- Different toxicities (↓overlapping toxicities)
- Each drug effective by itself
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Cell-Cycle Drug Effects
1.
Cell-cycle phase-specific drugs:
Must be present for an extended time → given by infusions
or in frequent small doses.
G1-phase specific: Asparaginase (Enzyme).
S-phase
specific:
Methotrexate,
Fluorouracil,
Mercaptopurine (Antimetabolites).
G2-phase specific: Bleomycin (Antitumor antibiotic)
M-phase specific: Vinca alkaloids (Vincristine, Vinblastine)
(Mitotic inhibitors).
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2. Cell-cycle phase non-specific drugs (cyclespecific):
Act during any phase including G0. More toxic to proliferating
cells than G0 cells.
cyclophosphamide. Carmustine: Alkylating agents.
Cisplatin, Carboplatin: Platinium compds.
Doxorubicin: Antitumor antibiotics.
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Toxicity to malignant tissues & normal tissues with↑
growth fraction
(bone marrow – GIT epithelium – hair follicles – sperm-forming cells)
 Myelosuppression “most common”
Neutropenia, Thrombocytopenia, Anemia.
 GIT Toxicities
Nausea & Vomiting
GI mucosal irritation (stomatitis, diarrhea)
 Dermatologic Disorders:
Alopecia, Extravasation, Photosensitivity.
 Infertility
 Tumor Lysis Syndrome (TLS):
Massive cell death & DNA degradation → hyperuricemia → renal injury
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Unique toxicities
A. Cardiotoxicity: Doxorubicin
B. Nephrotoxicity: Cisplatin & Methotrexate.
C. Pulmonary Toxicity: Bleomycin.
D. Hepatotoxicity: Asparaginase
E. Hemorrhagic cystitis: Cyclophosphamide → acrolein
F. Neurotoxicity: Vincristine, Cisplatin.
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
Combat chemotherapy-induced toxicity
(granulocyte colony-stimulating factor)
↓ duration and depth of neutropenia after chemotherapy
(↓xanthine oxidase)
Management of hyperuricemia
(dexamethasone + ondansetron - rantidine? - strong anti-emetic)
↓ hypersensitivity
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treatment of acrolein induced hemorrhagic cystitis
reduces toxicity of methotrexate to normal cells.
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ERA & PRA
Estrogen Receptor Assay
Progesterone Receptor Assay
 Lab test done to find out if cancer cells have estrogen
(progesterone) receptors
 Cells with ERs need E to grow while cells with PRs need P
to grow.
 ER+  growth of cancer cells is E-dependant
ER¯  growth of cancer cells is E-independent
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Tumor markers
Tumor markers are substances found in blood, urine and
tissues, produced by tumor cells or by other body cells in
response to cancer or certain benign conditions.
An elevated level of a tumor marker can indicate cancer;
however, there can also be other causes of the elevation.
Tumor marker levels are checked at the time of diagnosis;
before, during, and after therapy; and then periodically to
monitor for recurrence.
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Tumor Marker
Associated Tumor
CEA
Carcinoembryonic
Antigen
GIT, BREAST, LUNG
CANCERS
CA-125
Cancer Antigen-125
OVARIAN CANCER
PSA
Prostate Specific
Antigen
PROSTATE CANCER
β-HCG
Human Chorionic
Gonadropin
TESTICULAR CANCER
AFP
Alpha-fetoprotein
LIVER CANCER
Tg
Thyroglobulin
THYROID CANCER
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If a man has ↑ PSA level
 Search for PC
If a person has ↑ β-HCG level
 Search for testicular cancer
If a person has ↑ AFP level
 Search for liver cancer
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M0 means…
 No distant metastasis
Nx means…
 Lymph nodes not assessed
Mx means….
 Distant metastasis not assessed