Ch 11 Cancer Screening

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Cancer Screening and Diagnosis

Surgery, Radiation, and Chemotherary

Emerging Treatments: Immunotherapy and Molecular Targeting

Clinical Trials and Other Approaches

Contents

Chapter 11

Cancer Screening, Diagnosis, and Treatment

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Cancer Screening and DiagnosisCancer Screening and Diagnosis

►Cancer treatment success or not are Cancer treatment success or not are strongly influenced by the stage of strongly influenced by the stage of diagnosisdiagnosis

►F. 11-1F. 11-1►Many cancers are difficult to detectMany cancers are difficult to detect

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Cancer has few symptoms that arise early or are Cancer has few symptoms that arise early or are specific for the diseasespecific for the disease

► The location of symptoms varies widely, The location of symptoms varies widely, depending on the type of cancer involveddepending on the type of cancer involved

► Small and localized: no symptomsSmall and localized: no symptoms► The warning signs of cancerThe warning signs of cancer

Change in bowel or bladder habitsChange in bowel or bladder habits A sore that dose not healA sore that dose not heal Unusual bleeding or dischargeUnusual bleeding or discharge Thickening or lump in the breast or elsewhereThickening or lump in the breast or elsewhere Indigestion or difficulty swallowingIndigestion or difficulty swallowing Obvious change in a wart or moleObvious change in a wart or mole Nagging cough or hoarsenessNagging cough or hoarseness

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►Two shortcomingsTwo shortcomings Symptoms appear too lateSymptoms appear too late None of the listed symptoms is specific for None of the listed symptoms is specific for

cancercancer

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The pap smear illustrates that early detection can The pap smear illustrates that early detection can prevent cancer deathsprevent cancer deaths

►Pap smear is a procedure for the early Pap smear is a procedure for the early detection of the uterine cervix cancer detection of the uterine cervix cancer (1930s)(1930s)

►F. 11-2F. 11-2►BiopsyBiopsy►DNA test for HPVDNA test for HPV

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Mammography is an image technique used in Mammography is an image technique used in screening for early stage breast cancersscreening for early stage breast cancers

► Screening procedures for early breast canScreening procedures for early breast cancer by X-ray : mammographycer by X-ray : mammography

► Benefits for two groups of individualsBenefits for two groups of individuals High risk groupHigh risk group Over 50 y/o women Over 50 y/o women

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Colonoscopy, X-ray procedures, and the fecal Colonoscopy, X-ray procedures, and the fecal occult blood test are used in screening for early occult blood test are used in screening for early

stage colorectal cancersstage colorectal cancers► Colonoscopy:Colonoscopy:

ColonoscopeColonoscope 6-9 inches6-9 inches To see inner surface of the colonTo see inner surface of the colon BiopsyBiopsy

► X-ray imaging techniques: barium enemaX-ray imaging techniques: barium enema Still not as accurate as colonoscopy in detecting early cancersStill not as accurate as colonoscopy in detecting early cancers Vittual colonoscopy: new procedures by take pictures at various Vittual colonoscopy: new procedures by take pictures at various

anglesangles► Fecal occult blood test (FOBT)Fecal occult blood test (FOBT)

Not sensitive and specific for screening colorectal cancers Not sensitive and specific for screening colorectal cancers ► APC gene mutationAPC gene mutation

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Blood tests for cancer screening include the PSA Blood tests for cancer screening include the PSA test for prostate cancer as well as experimental test for prostate cancer as well as experimental

new proteomic techniquesnew proteomic techniques► Blood test is a simple methodBlood test is a simple method► PSA test: for over 50 y/o manPSA test: for over 50 y/o man

Prostate-specific antigen (PSA) measurementProstate-specific antigen (PSA) measurement PSA normally produce by the prostate glandPSA normally produce by the prostate gland By infection, hyperplasia, or cancer, the PSA concentration will iBy infection, hyperplasia, or cancer, the PSA concentration will i

ncreasencrease Blood test also be use as a tracer for cancer therapyBlood test also be use as a tracer for cancer therapy

► Others protein related with cancersOthers protein related with cancers Alpha-fetoprotein: by some liver cancerAlpha-fetoprotein: by some liver cancer Carcinoembryonic antigen (CEA): by some colon, stomach, pancCarcinoembryonic antigen (CEA): by some colon, stomach, panc

reatic, and lung cancersreatic, and lung cancers CA125: ovarian cancerCA125: ovarian cancer

► Proteomic analysis for blood protein analysis (F. 11-3)Proteomic analysis for blood protein analysis (F. 11-3)

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False negatives, false positives, and overdiagnosis False negatives, false positives, and overdiagnosis are some of the problems encountered with cancer are some of the problems encountered with cancer

screening testsscreening tests► ObjectivesObjectives

Early detectionEarly detection Sensitivity and specificitySensitivity and specificity

► F. 11-4F. 11-4► FOBT: 98% specificity (2% false positives)FOBT: 98% specificity (2% false positives)► overdiagnosisoverdiagnosis

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A biopsy can diagnose the presence of cancer A biopsy can diagnose the presence of cancer before invasion and metastasis have begunbefore invasion and metastasis have begun

►Biopsy specimen can measure the Biopsy specimen can measure the exact nature of cancerexact nature of cancer Brain specimen is difficult to obtainBrain specimen is difficult to obtain

► Imaging techniquesImaging techniques X-rayX-ray CT scanCT scan MRIMRI Ultrasound imagingUltrasound imaging

►F. 11-5F. 11-5

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Cancer diagnosis includes information regarding Cancer diagnosis includes information regarding the stage of the diseasethe stage of the disease

► How far a person’s cancer has progresseHow far a person’s cancer has progressed? (tumor stages?)d? (tumor stages?)

► Dysplasia analysisDysplasia analysis

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Cancer diagnosis includes information regarding Cancer diagnosis includes information regarding the microscopic appearance and molecular the microscopic appearance and molecular

properties of the tumor cellsproperties of the tumor cells► Diagnosis information: important for cancDiagnosis information: important for canc

er behavior and treated methodser behavior and treated methods Cancer’s site of origin (in situ or not)Cancer’s site of origin (in situ or not) Cell type involved: tumor gradingCell type involved: tumor grading

► Molecular components analysis: mechaniMolecular components analysis: mechanismsm DNA microarrayDNA microarray Oncotype DX test: measure 21 key genes relatOncotype DX test: measure 21 key genes relat

ed breast cancer metastasis (F. 11-6)ed breast cancer metastasis (F. 11-6)

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Surgery, Radiation, and ChemotherapySurgery, Radiation, and Chemotherapy

►A variety of treatment options for A variety of treatment options for cancer therapycancer therapy

►Depend onDepend on Cancer typeCancer type Spread situationSpread situation

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Surgery can cure cancers when they have not yet Surgery can cure cancers when they have not yet metastasizedmetastasized

► Bacterial infectionBacterial infection► In 1890, mastectomyIn 1890, mastectomy

Breast cancer: complete removal of the breast cancerBreast cancer: complete removal of the breast cancer► In 1900s: surgical techniques established for remIn 1900s: surgical techniques established for rem

ove tumorsove tumors► New techniquesNew techniques

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

► Surgical removal of the primary tumor is frequenSurgical removal of the primary tumor is frequently followed by radiation, chemotherapy, or bothtly followed by radiation, chemotherapy, or both

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Radiation therapy kills cancer cells by triggering Radiation therapy kills cancer cells by triggering apoptosis or mitotic deathapoptosis or mitotic death

► In some cases, surgery is not even practicIn some cases, surgery is not even practicalal brain tumorbrain tumor LeukemiasLeukemias

► Radiation therapyRadiation therapy High-energy X-raysHigh-energy X-rays Ionizing radiationsIonizing radiations

► Apoptosis and mitotic deathApoptosis and mitotic death

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Radiation treatment are designed to minimize Radiation treatment are designed to minimize damage to normal tissuesdamage to normal tissues

► Radiation planningRadiation planning► Allowing maximum radiation to be directed at tAllowing maximum radiation to be directed at t

he tumor area with minimal exposure to surrouhe tumor area with minimal exposure to surrounding tissuesnding tissues

► Fig. 11-7Fig. 11-7► Brachytherapy: using radiation source directly iBrachytherapy: using radiation source directly i

nsert within the tumornsert within the tumor► Radiation + anticancer drugsRadiation + anticancer drugs► HyperthermiaHyperthermia

Combination of radiation and hyperthermiaCombination of radiation and hyperthermia Table 11-1Table 11-1

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Surgery, Radiation, and Chemotherapy

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Chemotherapy involves the use of drugs that circulate Chemotherapy involves the use of drugs that circulate in the bloodstream to reach cancer cells wherever they in the bloodstream to reach cancer cells wherever they

may residemay reside►Drugs for inhibition cancer cells Drugs for inhibition cancer cells

proliferationproliferation►Suiting for metastasized cancerSuiting for metastasized cancer►For a wide range of cancersFor a wide range of cancers►Table 11-2Table 11-2

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Drugs for chemotherapyDrugs for chemotherapy► Antimetabolites: disrupting DNA synthesis by suAntimetabolites: disrupting DNA synthesis by su

bstituting for molecules involved in normal metbstituting for molecules involved in normal metabolic pathways (F. 11-8, 11-9)abolic pathways (F. 11-8, 11-9)

► Alkylating and platinating drugs: by crosslinking Alkylating and platinating drugs: by crosslinking DNA (F. 11-10)DNA (F. 11-10)

► Antibiotics and plant-derived drugsAntibiotics and plant-derived drugs Streptomyces group:dexorubicin, daunorubicin, mitoStreptomyces group:dexorubicin, daunorubicin, mito

mycin, bleomycinmycin, bleomycin Plant source of drugs: etoposide, teniposidePlant source of drugs: etoposide, teniposide

► Targeting to DNA moleculesTargeting to DNA molecules► Topoisomerase inhibitionTopoisomerase inhibition► Microtubules inhibitor: taxolMicrotubules inhibitor: taxol

► Hormones : for hormone-dependent cancerHormones : for hormone-dependent cancer

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Hormone therapyHormone therapy

► In 1940s, Charles HugginsIn 1940s, Charles Huggins► For prostate cancer patientsFor prostate cancer patients► Depending on androgens (one type of testosteronDepending on androgens (one type of testosteron

e)e)► Drugs for blocking hormones production or actionDrugs for blocking hormones production or action► Gonadotropins for androgen productionGonadotropins for androgen production

Leuprolide: an analog of the gonadotropin-releasing horLeuprolide: an analog of the gonadotropin-releasing hormone to inhibit androgen productionmone to inhibit androgen production

► Breast cancer: estrogen familyBreast cancer: estrogen family Breast cancer is estrogen requirementBreast cancer is estrogen requirement Tamoxifen: blocking estrogen action (F. 11-11)Tamoxifen: blocking estrogen action (F. 11-11)

► Binding with estrogen receptors for prevention activationBinding with estrogen receptors for prevention activation► Lymphocytic cancers: glucocorticoidsLymphocytic cancers: glucocorticoids

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Toxic side effects and drug resistance can limit the Toxic side effects and drug resistance can limit the effectiveness of chemotherapyeffectiveness of chemotherapy

► The most serious side effects of chemotherapy iThe most serious side effects of chemotherapy involve the gastrointestinal tract and the bone mnvolve the gastrointestinal tract and the bone marrowarrow

► Radiation therapyRadiation therapy Damage to dividing cellsDamage to dividing cells Nausea, vomiting, diarrhea, anemia, defective blood Nausea, vomiting, diarrhea, anemia, defective blood

clotting, immune deficiencyclotting, immune deficiency► Drug resistanceDrug resistance

Multidrug resistance transport proteinsMultidrug resistance transport proteins Cancer stem cellsCancer stem cells

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Combination chemotherapy and stem cell transplants Combination chemotherapy and stem cell transplants are two strategies for improving the effectiveness of are two strategies for improving the effectiveness of

chemotherapy chemotherapy

► Two strategyTwo strategy Several drugs combination: combination cheSeveral drugs combination: combination che

motherapymotherapy►BEP chemotherapy: bleomycin, etoposide, plantinBEP chemotherapy: bleomycin, etoposide, plantin

ol (for testicular cancer)ol (for testicular cancer)►CMF chemotherapy: cyclophosphamide, methotreCMF chemotherapy: cyclophosphamide, methotre

xate, fluorouracil (for breast cancer)xate, fluorouracil (for breast cancer) Stem cell transplantation (bone marrow transStem cell transplantation (bone marrow trans

plantation) for high dose chemotherapy persoplantation) for high dose chemotherapy person n

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Molecular and genetic testing is beginning to allow Molecular and genetic testing is beginning to allow cancer treatments to be tailored to individual patientscancer treatments to be tailored to individual patients

► Designing drug treatments for each indiviDesigning drug treatments for each individual patientdual patient

► DNA microarrayDNA microarray► Example: IressaExample: Iressa

EGF receptor inhibitorEGF receptor inhibitor For lung cancer therapyFor lung cancer therapy Tumor shrinkage occurs in only about 10% paTumor shrinkage occurs in only about 10% pa

tient (but this drug works extremely well)tient (but this drug works extremely well) F. 11-12F. 11-12

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Emerging treatments: immunotherapy and Emerging treatments: immunotherapy and molecular targetingmolecular targeting

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Immunotherapies exploit the ability of the immune Immunotherapies exploit the ability of the immune system to recognize cancer cellssystem to recognize cancer cells

► Immunotherapy was first proposed in Immunotherapy was first proposed in 1800s1800s

►Using live or dead bacteria to provoke the Using live or dead bacteria to provoke the immune system of cancer patientsimmune system of cancer patients

►BCG bacteria for prolong activation of BCG bacteria for prolong activation of immune after bladder cancer surgery immune after bladder cancer surgery patientspatients

►Cytokines: are proteins produced by body Cytokines: are proteins produced by body to stimulate immune responses against to stimulate immune responses against agentsagents interferon alpha for cancer therapyinterferon alpha for cancer therapy IL-2, TNFIL-2, TNF

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Large quantities of identical antibody molecules Large quantities of identical antibody molecules can be produced using the monoclonal antibody can be produced using the monoclonal antibody

techniquetechnique►BCG and cytokines are nonspecific BCG and cytokines are nonspecific

approaches to immunotherapyapproaches to immunotherapy►Monoclonal antibodies (F. 11-13)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 Monoclonal antibodies can be used to trigger cancer cell destruction either by themselves or linked to cell destruction either by themselves or linked to

radioactive substancesradioactive substances

►F. 11-14F. 11-14►Some problemsSome problems

Abs from mice: cannot be used for Abs from mice: cannot be used for repeated treatmentrepeated treatment

Cancer cells antigen may be present on Cancer cells antigen may be present on normal cellnormal cell

►F. 11-15 F. 11-15

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Several types of cancer vaccines are currently Several types of cancer vaccines are currently under developmentunder development

► Cell-mediated immunity: cytotoxic T lympCell-mediated immunity: cytotoxic T lymphocyteshocytes

► Cancer vaccine development Cancer vaccine development

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Adoptive-cell-transfer (ACT) therapy uses a persoAdoptive-cell-transfer (ACT) therapy uses a person’s own antitumor lymphocytes that have been seln’s own antitumor lymphocytes that have been sel

ected and grown in the laboratory ected and grown in the laboratory

►ACT therapy: lymphocytes → isolation ACT therapy: lymphocytes → isolation → selection → grown in Lab. → enhance → selection → grown in Lab. → enhance cancer-fighting properties → injecting cancer-fighting properties → injecting into body (at cancer production site)into body (at cancer production site)

►F. 11-16F. 11-16

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Herceptin and gleevec are anticancer drugs that illHerceptin and gleevec are anticancer drugs that illustrate the concept of molecular targetingustrate the concept of molecular targeting

► Mutation gene → mutation protein → molMutation gene → mutation protein → molecular targeting by drugecular targeting by drug

► Herceptin Ab: Binding and inactivates ErbHerceptin Ab: Binding and inactivates ErbB2 receptorB2 receptor 25% breast and ovarian cancers have amplifie25% breast and ovarian cancers have amplifie

d ERBB2 gene → ErbB2 receptor overexpressid ERBB2 gene → ErbB2 receptor overexpressionon

► Gleevec (a drug): a inhibitor for tyrosine kiGleevec (a drug): a inhibitor for tyrosine kinase by nase by BCR-ABLBCR-ABL gene gene

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

►Table 11-3Table 11-3

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Anti-angiogenic therapy illustrates the difficulties iAnti-angiogenic therapy illustrates the difficulties involved in translating laboratory research into humnvolved in translating laboratory research into hum

an cancer treatmentsan cancer treatments► Angiogenesis inhibitor for cancer therapyAngiogenesis inhibitor for cancer therapy► Judah Folkman used angiostatin and endostatin (angioJudah Folkman used angiostatin and endostatin (angio

genesis-inhibiting proteins) (F. 3-6)genesis-inhibiting proteins) (F. 3-6)► Anti-angiogenic therapy may work better at earlier stagAnti-angiogenic therapy may work better at earlier stag

es of canceres of cancer► The optimal dose for angiogenesis-inhibiting drugs may The optimal dose for angiogenesis-inhibiting drugs may

need to be trailored to each individual patientneed to be trailored to each individual patient► Angiogenesis inhibitors may work best when their conceAngiogenesis inhibitors may work best when their conce

ntration within the body is maintained at a relatively contration within the body is maintained at a relatively constant levelnstant level

► Its function only stop tumors becoming largerIts function only stop tumors becoming larger► In 2004, Avastin became the first-angiogenic drugIn 2004, Avastin became the first-angiogenic drug

A monoclonal antibodiesA monoclonal antibodies VEGF inhibitorVEGF inhibitor

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Tumor Angiogenesis

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Engineered viruses are potential tools for repairing Engineered viruses are potential tools for repairing or killing cancer cellsor killing cancer cells

► Gene therapyGene therapy► F. 11-7F. 11-7► Viruses cause human cells rupture and die:Viruses cause human cells rupture and die:

lysis lysis ONYX-015: an adenovirusONYX-015: an adenovirus Mutation to replicate only in cells with a defecMutation to replicate only in cells with a defec

tive p53 pathway (F. 11-18)tive p53 pathway (F. 11-18)

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Clinical trials and other approachesClinical trials and other approaches

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Human clinical trials involve multiple phases of Human clinical trials involve multiple phases of testingtesting

► F. 11-19F. 11-19► Phase III: radomized and double-blind traiPhase III: radomized and double-blind trai

ll PlaceboPlacebo

► Phase IV: side effectsPhase IV: side effects

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Complementary and alternative cancer treatments Complementary and alternative cancer treatments are frequently used by people who have cancerare frequently used by people who have cancer

► Complementary treatmentComplementary treatment Herbal remediesHerbal remedies VitaminsVitamins Special dietSpecial diet Pshysical and psychological practicesPshysical and psychological practices

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Psychological factors are not a significant cause of Psychological factors are not a significant cause of cancer but may influence the course of the diseasecancer but may influence the course of the disease

Documents

Ch 11 Cancer Screening