Chapter 11 Cancer Screening, Diagnosis, and Treatment

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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
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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

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Cancer Screening and Diagnosis
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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

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• Two shortcomings
• Symptoms appear too late
• None of the listed symptoms is specific for cancer

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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

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Cancer Screening and Diagnosis
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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

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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

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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.
  11-3)

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Cancer Screening and Diagnosis
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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

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Cancer Screening and Diagnosis
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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 techniques
• X-ray
• CT scan
• MRI
• Ultrasound imaging
• F. 11-5

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Cancer Screening and Diagnosis
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Cancer diagnosis includes information regarding
the stage of the disease

• How far a persons cancer has progressed? (tumor
  stages?)
• Dysplasia analysis

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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)

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Cancer Screening and Diagnosis
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Surgery, Radiation, and Chemotherapy

• A variety of treatment options for cancer therapy
• Depend on
• Cancer type
• Spread situation

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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

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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

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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

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Surgery, Radiation, and Chemotherapy
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Surgery, Radiation, and Chemotherapy
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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

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Surgery, Radiation, and Chemotherapy
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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 groupdexorubicin, daunorubicin,
  mitomycin, bleomycin
• Plant source of drugs etoposide, teniposide
• Targeting to DNA molecules
• Topoisomerase inhibition
• Microtubules inhibitor taxol
• Hormones for hormone-dependent cancer

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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-releasin
  g 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

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Surgery, Radiation, and Chemotherapy
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Surgery, Radiation, and Chemotherapy
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Surgery, Radiation, and Chemotherapy
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Surgery, Radiation, and Chemotherapy
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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

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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

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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

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Surgery, Radiation, and Chemotherapy
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Emerging treatments immunotherapy and molecular
targeting
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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

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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)

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Emerging Treatments Immunotherapy and Molecular
Targeting
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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

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Emerging Treatments Immunotherapy and Molecular
Targeting
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Emerging Treatments Immunotherapy and Molecular
Targeting
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Several types of cancer vaccines are currently
under development

• Cell-mediated immunity cytotoxic T lymphocytes
• Cancer vaccine development

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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

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Emerging Treatments Immunotherapy and Molecular
Targeting
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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

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A diverse group of potential targets for
anticancer drugs are currently being investigated

• Table 11-3

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Emerging Treatments Immunotherapy and Molecular
Targeting
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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

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Tumor Angiogenesis
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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)

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Emerging Treatments Immunotherapy and Molecular
Targeting
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Emerging Treatments Immunotherapy and Molecular
Targeting
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Clinical trials and other approaches
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Human clinical trials involve multiple phases of
testing

• F. 11-19
• Phase III radomized and double-blind trail
• Placebo
• Phase IV side effects

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Clinical Trials and Other Approaches
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Complementary and alternative cancer treatments
are frequently used by people who have cancer

• Complementary treatment
• Herbal remedies
• Vitamins
• Special diet
• Pshysical and psychological practices

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Clinical Trials and Other Approaches
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Psychological factors are not a significant cause
of cancer but may influence the course of the
disease