Chapter 11

Cancer Screening, Diagnosis, and Treatment

Contents
Cancer Screening and Diagnosis
Surgery, Radiation, and Chemotherary
Emerging Treatments: Immunotherapy and Molecular Targeting
Clinical Trials and Other Approaches

Cancer Screening and Diagnosis

Cancer

treatment success or not are

strongly influenced by the stage of
diagnosis
F. 11-1
Many cancers are difficult to detect

Cancer Screening and Diagnosis

Cancer has few symptoms that arise early or are

specific for the disease
The

location of symptoms varies widely,

depending on the type of cancer involved
Small and localized: no symptoms
The warning signs of cancer

Change in bowel or bladder habits

A sore that dose not heal
Unusual bleeding or discharge
Thickening or lump in the breast or elsewhere
Indigestion or difficulty swallowing
Obvious change in a wart or mole
Nagging cough or hoarseness

 Two

shortcomings

Symptoms appear too late

None of the listed symptoms is specific for
cancer

The pap smear illustrates that early detection can

prevent cancer deaths
Pap

smear is a procedure for the early

detection of the uterine cervix cancer
(1930s)
F. 11-2
Biopsy
DNA test for HPV

Cancer Screening and Diagnosis

Mammography is an image technique used in

screening for early stage breast cancers
Screening

procedures for early breast

cancer by X-ray : mammography
Benefits for two groups of individuals
High risk group
Over 50 y/o women

Colonoscopy, X-ray procedures, and the fecal

occult blood test are used in screening for early
stage colorectal cancers

Colonoscopy:

Colonoscope
6-9 inches
To see inner surface of the colon
Biopsy

X-ray imaging techniques: barium enema

Still not as accurate as colonoscopy in detecting early
cancers
Vittual colonoscopy: new procedures by take pictures at
various angles

Fecal occult blood test (FOBT)

Not sensitive and specific for screening colorectal cancers

APC gene mutation

9

Blood tests for cancer screening include the PSA

test for prostate cancer as well as experimental
new proteomic techniques

Blood test is a simple method

PSA test: for over 50 y/o man
Prostate-specific antigen (PSA) measurement
PSA normally produce by the prostate gland
By infection, hyperplasia, or cancer, the PSA concentration
will increase
Blood test also be use as a tracer for cancer therapy

Others protein related with cancers

Alpha-fetoprotein: by some liver cancer
Carcinoembryonic antigen (CEA): by some colon, stomach,
pancreatic, and lung cancers
CA125: ovarian cancer

Proteomic analysis for blood protein analysis (F. 113)

10

Cancer Screening and Diagnosis

11

False negatives, false positives, and overdiagnosis

are some of the problems encountered with cancer
screening tests
Objectives
Early detection
Sensitivity and specificity
F.

11-4
FOBT: 98% specificity (2% false
positives)
overdiagnosis
12

Cancer Screening and Diagnosis

13

A biopsy can diagnose the presence of cancer

before invasion and metastasis have begun
Biopsy

specimen can measure the

exact nature of cancer
Brain specimen is difficult to obtain

Imaging

F.

techniques

X-ray
CT scan
MRI
Ultrasound imaging

11-5

14

Cancer Screening and Diagnosis

15

Cancer diagnosis includes information regarding

the stage of the disease
How

far a persons cancer has

progressed? (tumor stages?)
Dysplasia analysis

16

Cancer diagnosis includes information regarding

the microscopic appearance and molecular
properties of the tumor cells
Diagnosis information: important for
cancer behavior and treated methods
Cancers site of origin (in situ or not)
Cell type involved: tumor grading
Molecular

components analysis:
mechanism
DNA microarray
Oncotype DX test: measure 21 key genes
related breast cancer metastasis (F. 11-6)
17

Cancer Screening and Diagnosis

18

Surgery, Radiation, and Chemotherapy

A

variety of treatment options for

cancer therapy
Depend on
Cancer type
Spread situation

19

Surgery can cure cancers when they have not yet

metastasized
Bacterial

infection
In 1890, mastectomy
Breast cancer: complete removal of the breast cancer
In

1900s: surgical techniques established for

remove tumors
New techniques

Laser surgery
Electrosurgery: electrical current
Cryosurgery: liquid nitrogen
High-intensity focused ultrasound (HIFU)

Surgical

removal of the primary tumor is

frequently followed by radiation, chemotherapy,
or both

20

Radiation therapy kills cancer cells by triggering

apoptosis or mitotic death
In

some cases, surgery is not even

practical
brain tumor
Leukemias

Radiation

therapy

High-energy X-rays
Ionizing radiations
Apoptosis

and mitotic death

21

Radiation treatment are designed to minimize

damage to normal tissues
Radiation

planning
Allowing maximum radiation to be directed
at the tumor area with minimal exposure to
surrounding tissues
Fig. 11-7
Brachytherapy: using radiation source
directly insert within the tumor
Radiation + anticancer drugs
Hyperthermia
Combination of radiation and hyperthermia
Table 11-1

22

Surgery, Radiation, and Chemotherapy

23

Surgery, Radiation, and Chemotherapy

24

Chemotherapy involves the use of drugs that circulate

in the bloodstream to reach cancer cells wherever they
may reside
Drugs for inhibition cancer cells
proliferation
Suiting for metastasized cancer
For a wide range of cancers
Table 11-2

25

Surgery, Radiation, and Chemotherapy

26

Drugs for chemotherapy

Antimetabolites:

disrupting DNA synthesis

by substituting for molecules involved in
normal metabolic pathways (F. 11-8, 11-9)
Alkylating and platinating drugs: by
crosslinking DNA (F. 11-10)
Antibiotics and plant-derived drugs
Streptomyces group:dexorubicin, daunorubicin,
mitomycin, bleomycin
Plant source of drugs: etoposide, teniposide
Targeting

to DNA molecules
Topoisomerase inhibition
Microtubules inhibitor: taxol

Hormones

: for hormone-dependent cancer

27

Hormone therapy
In

1940s, Charles Huggins

For prostate cancer patients
Depending on androgens (one type of
testosterone)
Drugs for blocking hormones production or action
Gonadotropins for androgen production
Leuprolide: an analog of the gonadotropin-releasing
hormone to inhibit androgen production
Breast

cancer: estrogen family

Breast cancer is estrogen requirement

Tamoxifen: blocking estrogen action (F. 11-11)
Binding

with estrogen receptors for prevention activation

Lymphocytic

cancers: glucocorticoids
28

Surgery, Radiation, and Chemotherapy

29

Surgery, Radiation, and Chemotherapy

30

Surgery, Radiation, and Chemotherapy

31

Surgery, Radiation, and Chemotherapy

32

Toxic side effects and drug resistance can limit the

effectiveness of chemotherapy
The

most serious side effects of

chemotherapy involve the gastrointestinal
tract and the bone marrow
Radiation therapy
Damage to dividing cells
Nausea, vomiting, diarrhea, anemia, defective
blood clotting, immune deficiency
Drug

resistance

Multidrug resistance transport proteins

Cancer stem cells
33

Combination chemotherapy and stem cell transplants

are two strategies for improving the effectiveness of
chemotherapy
Two

strategy

Several drugs combination: combination

chemotherapy
BEP

chemotherapy: bleomycin, etoposide,

plantinol (for testicular cancer)
CMF chemotherapy: cyclophosphamide,
methotrexate, fluorouracil (for breast cancer)

Stem cell transplantation (bone marrow

transplantation) for high dose
chemotherapy person
34

Molecular and genetic testing is beginning to allow

cancer treatments to be tailored to individual patients
Designing

drug treatments for each

individual patient
DNA microarray
Example: Iressa
EGF receptor inhibitor
For lung cancer therapy
Tumor shrinkage occurs in only about 10%
patient (but this drug works extremely well)
F. 11-12
35

Surgery, Radiation, and Chemotherapy

36

Emerging treatments: immunotherapy and

molecular targeting

37

Immunotherapies exploit the ability of the immune

system to recognize cancer cells
Immunotherapy

was first proposed in 1800s

Using live or dead bacteria to provoke the
immune system of cancer patients
BCG bacteria for prolong activation of
immune after bladder cancer surgery
patients
Cytokines: are proteins produced by body to
stimulate immune responses against agents
interferon alpha for cancer therapy
IL-2, TNF
38

Large quantities of identical antibody molecules

can be produced using the monoclonal antibody
technique
BCG and cytokines are nonspecific
approaches to immunotherapy
Monoclonal antibodies (F. 11-13)

39

Emerging Treatments : Immunotherapy and Molecular Targeting

40

Monoclonal antibodies can be used to trigger cancer

cell destruction either by themselves or linked to
radioactive substances
F.

11-14
Some problems
Abs from mice: cannot be used for
repeated treatment
Cancer cells antigen may be present on
normal cell
F.

11-15

41

Emerging Treatments : Immunotherapy and Molecular Targeting

42

Emerging Treatments : Immunotherapy and Molecular Targeting

43

Several types of cancer vaccines are currently

under development
Cell-mediated

immunity: cytotoxic T

lymphocytes
Cancer vaccine development

44

Adoptive-cell-transfer (ACT) therapy uses a

persons own antitumor lymphocytes that have
been selected and grown in the laboratory
ACT

therapy: lymphocytes isolation

selection grown in Lab. enhance
cancer-fighting properties injecting
into body (at cancer production site)
F. 11-16

45

Emerging Treatments : Immunotherapy and Molecular Targeting

46

Herceptin and gleevec are anticancer drugs that

illustrate the concept of molecular targeting
Mutation

gene mutation protein

molecular targeting by drug
Herceptin Ab: Binding and inactivates
ErbB2 receptor
25% breast and ovarian cancers have
amplified ERBB2 gene ErbB2 receptor
overexpression
Gleevec

(a drug): a inhibitor for tyrosine

kinase by BCR-ABL gene
47

A diverse group of potential targets for anticancer

drugs are currently being investigated
Table

11-3

48

Emerging Treatments : Immunotherapy and Molecular Targeting

49

Anti-angiogenic therapy illustrates the difficulties

involved in translating laboratory research into
human cancer treatments

Angiogenesis inhibitor for cancer therapy

Judah Folkman used angiostatin and endostatin
(angiogenesis-inhibiting proteins) (F. 3-6)
Anti-angiogenic therapy may work better at earlier
stages of cancer
The optimal dose for angiogenesis-inhibiting drugs
may need to be trailored to each individual patient
Angiogenesis inhibitors may work best when their
concentration within the body is maintained at a
relatively constant level
Its function only stop tumors becoming larger
In 2004, Avastin became the first-angiogenic drug
A monoclonal antibodies
VEGF inhibitor

50

Tumor Angiogenesis

51

Engineered viruses are potential tools for repairing

or killing cancer cells
Gene

therapy
F. 11-7
Viruses cause human cells rupture and
die: lysis

ONYX-015: an adenovirus
Mutation to replicate only in cells with a
defective p53 pathway (F. 11-18)

52

Emerging Treatments : Immunotherapy and Molecular Targeting

53

Emerging Treatments : Immunotherapy and Molecular Targeting

54

Clinical trials and other approaches

55

Human clinical trials involve multiple phases of

testing
F.

11-19
Phase III: radomized and double-blind
trail
Placebo
Phase

IV: side effects

56

Clinical Trials and Other Approaches

57

Complementary and alternative cancer treatments

are frequently used by people who have cancer
Complementary

treatment

Herbal remedies
Vitamins
Special diet
Pshysical and psychological practices

58

Clinical Trials and Other Approaches

59

Psychological factors are not a significant cause of

cancer but may influence the course of the disease

60