cancer final review

8/7/2019 cancer final review

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Cancer Concepts Winter, 2011

Final Review

CC-Pieters & Liebmann Feb 11 2011


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What Well Try to Cover:ImportantPoints to Know

What agents can cause cancer? How do cancer cells develop from normal cells?

What is the difference between hyperplasia, metaplasia, dysplasia, carcinoma in situ,

invasive cancer, and neoplasia?

What is an oncogene? Know some examples of oncogenes and how they function.

What is a tumor suppressor gene? Know some examples of tumor suppressor genesand how the function.

What pathologic changes do cells undergo as they transform from normal to cancer?

What are protein kinases?

What is involved in the process of metastasis?

a s ang ogenes s an w y o cancers nee Do cancer metastases pop up randomly? If not, know some sites that some tumors like

to go to.

What are the ma or reasons that sur er is used when a roachin cancer?

What are the major reasons that radiation is used when approaching cancer?

What are the major reasons that drugs are used when approaching cancer?CC-Pieters & Liebmann Feb 11 2011


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What Well Try to Cover:ImportantPoints to Know continued

Have a general understanding of chemotherapy drugs by class alkylators, anti-

metabolites, topoisomerase inhibitors, microtubule binding drugs, platinum

analogues, immune therapies, antibodies, tyrosine kinase inhibitors, others

What is the role of palliative care in cancer treatment? What interventions work to revent cancer? How do the work?

What cancer screening techniques are effective? What makes a cancer screen an

effective screen?

What is the difference between stage and grade of cancer? Have a general sense of

s ages o cancer How is pediatric oncology different from adult oncology?

What long term health issues might survivors of cancer have to deal with?

How can ou explain differences in the incidence of cancer around the world?



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Agents That Cause Cancer

Chemical Tobacco, Solvents, Pesticides

Physical Asbestos, Chronic Irritation

Radiation UV, Ionizing Viral HPV, HIV, EBV, HTLV-I

Bacterial H.Pylori

Parasitic Schistosomes, Liver Flukes

Think about how these cause cancer!



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ow o ancer e s eve opFrom Normal Cells?

Acquisition of Genetic Changes

Loss of Tumor Suppressor Function

Common TP53, Rb

Common TEL, EGFR, HER2, KRAS, MYC, etc.

Mor holo ic Chan es

Normal Hyperplasia Dysplasia CIS

Invasion



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at s t e erence etweenhyperplasia, metaplasia, dysplasia,

, ,and neoplasia?

yperp as a ncrease n um er o e s

Metaplasia Transformation of One Cell Type Into

Another Dysplasia Abnormal Development of Cells

Carcinoma in situMalignant Cells That Have NotInvaded Into Tissue

Invasive Cancer Malignant Cells That Have InvadedInto Tissue and Can Spread Further

Neo lasia New Cell Growth Does Not NecessarilRefer to Benign or Malignant



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What is an oncogene?Know some examples of oncogenes

an ow t ey unct on.-

Normal Cell Growth

Normal Functions:

Growth Factors (sisB Chain of PDGF)

Receptors (erb-2HER2, EGFR)

Intracellular Signal Transduction (src, abl, KRAS)

Nuclear Transcription Factors (myc, hox)



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Know some examples of tumor

function.

Normal Function Blocks Cell Proliferation

Normal Function Leads To DNA Repair Normal Function Leads to Apoptosis

Examples Rb, TP53, APC



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undergo as they transform from

Morphologic Changes

Normal Hyperplasia Dysplasia CIS

Invasion

Pleomorphism

Condensed Chromatin

Loss of Polarit

Anchorage Independent Growth

Loss of Contact Inhibition CC-Pieters & Liebmann Feb 11 2011


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What Are Protein Kinases?

Kinases add phosphate (PO3=) to proteins

acids that are phosphorylated

Lar e MW=80 char ed PO = inducesconformational change on protein

Conformational change affects protein

function

ATP or GTP are PO3= donors

Protein kinases are drug targetsCC-Pieters & Liebmann Feb 11 2011


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What is involved in the process ofmetastasis?

Cellular DiscohesionCells arenormally anchored to basementmembranes, the extra-cellular matrix, and adjacent cells. These

.

Invasion Through Basement Membrane The basement membrane mustbe destroyed. This will require enzymes. To get through the basement

membrane, theremust be cell motility. .

Survival in Blood/Lymph The cancer cell must avoid immune surveillance

Exit From Blood/Lymphatic Vessel See Invasion intoblood/lymphaticvessel

Growth in Foreign Soil Metastasis necessarily means the ability to growin an environment that is foreign to the one the cell originated in. Theremust be an ability to tolerate and thrive in new conditions.

Recruitment of New Vasculature In the absence of blood vessels, growtho a co ony o ce s s m e y e us on o oxygen an nu r en s.



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a s ang ogenes s an w y ocancers need it?

450 m Hepatoma Cell

Spheroid

Green Cells At Rim Are Viable

Red Cells in Center are

Necrotic

NO Blood Flow = NO Life

Molecular Therapy(2009) 17 8, 14041410CC-Pieters & Liebmann Feb 11 2011


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cancers need it?

Degradation of Basement

Membrane of Existing

Vessel

Migration of Endothelial

Cells into Interstitium

Endothelial Cell Proliferation

Lumen Formation

Generation of New

Basement Membrane

Fusion of Newly Formed

VesselsCC-Pieters & Liebmann Feb 11 2011


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Do cancer metastases pop uprandomly? If not, know some sites

a some umors e o go o.

Cancer Metastases Do NOT Appear at Random

Preferred Sites of Spread for Selected Cancers:

Lung Cancer: Bones, Liver, Adrenal Glands, Brain

, , ,

Colon Cancer: Liver, Abdominal Cavity, Lungs

Prostate Cancer: Bones

Pancreatic Cancer: Liver, Abdominal Cavity Renal Cell Carcinoma: Lungs, Bones, Brain



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at are t e ma or reasons t atsurgery is used when approaching

Biopsy for Diagnosis

Complete Resection for Cure

R0: Complete Resection, Negative Margins : ross y omp e e esec on,

Microscopically Positive Margins

R2: Grossly Incomplete Resection

Metastatectomy Possibly for ?Cure?

Palliation Relief of Obstruction, Bleeding, Pain, etc.



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What are the major reasons thatradiation isused when approaching

cancer? Radical Radiation for Cure

Adjuvant Radiation After Surgery

Improve Local Control Improve Survival

Palliative Radiation

Control Bleeding

O en Airwa s

?Prolong Life? (Cranial Radiation for Mets)



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at are t e ma or reasons t at rugsare used when approaching cancer?

Curative Chemotherapy

Leukemia, Lymphoma, Germ Cell Cancer

Adjuvant Chemotherapy Improve Survival After Surgical Resection

Improve Survival When Given With Radiation

a a ve emo erapy Relieve Pain, Dyspnea, Performance Status



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Have a general understanding ofchemotherapy drugs by class

alkylators, anti-metabolites,topoisomerase inhibitors, microtubulen ng rugs, p a num ana ogues,

immune therapies, antibodies, tyrosine,

ec an sm o c on Metabolism

Toxicity



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asses an ec an sms oChemotherapy Drugs

Alkylators: Cyclophosphamide, Nitrogen Mustard

Anti-metabolites: Fluorouracil (Capecitabine),

Cytarabine, Gemcitabine, Methotrexate, Fludarabine opo somerase n ors: oxoru c n, opos e,

Irinotecan

Microtubule Bindin Dru s: Vincas Taxanes



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asses an ec an sms oChemotherapy Drugs

Immune Thera ies: Interferon IL-2

Antibodies: Trastuzumab, Cetuximab, Rituximab

TK Inhibitors: Erlotinib, Sunitinib, Lapatinib Platinum Compounds: Cisplatin, Carboplatin,

Oxaliplatin

ormona gen s: amox en, roma ase n ors(Anastrazole), LHRH Agonists



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Metabolism of Chemotherapy Drugs

Primarily Renal Platinum Analogues, Methotrexate,

Bleomycin

Primarily Hepatic Taxanes, Vincas, Anthracyclines,

,

Primarily Intracellular 5-FU, Gemcitabine,

Cytarabine, Fludarabine

Also Prodrugs Cyclophosphamide, Capecitabine, Irinotecan,



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Toxicity of Chemotherapy Drugs

Myelosuppression Common

xcept ons: ncr st ne, eomyc n, s,

Antibodies, Cisplatin

, ,

Nitrosureas

Renal Cisplatin

Neurotoxicity Vincristine, Taxanes, Cis-/Oxalo-platin

,



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What is the role of palliative carein cancer treatment?

not just at the end

Relieve s m toms of disease and treatment

Focus on prognosis



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cancer? How do they work?

Tobacco Cessation

Diet and Cancer

No evidence for supplements

Surgery to Prevent Cancer n cancer am y syn romes

Drugs to Prevent Cancer

Finasteride: Prostate Cancer

,

Vaccines to Prevent Cancer

Hepatitis B: Hepatocellular Cancer

Pa illoma Viruses: Cervical Head and Neck Cancers



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effective? What makes a cancer

Definitely Effective Screens

Colonoscopy, Fecal Occult Blood for Colorectal Cancer

Pap Smear for Cervical Cancer Maybe Useful Screens

Chest CT in Smokers for Lung Cancer

Liver Scan/AFP in HB/CV(+) for Hepatoma

Definition of Effective Screen Reduces Morbidity and Mortality of Screened Cancer,



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of cancer? Have a general sense of stages ofcancer.

Staging

Films, Physical Exam

Grading

Histology

Strong Prognostic Value

Strong Therapeutic Value

Some Prognostic Value

Little Therapeutic Value

Uses T, N, M System Uses Morphologic Guidelines



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Staging Generalities

Stage I Small Tumor, Negative Nodes

Stage II Larger Tumor or Tumor Invades Deeper

Structures, Negative Nodes or Only Immediate Nodal

Grou

Stage III Larger Tumor or Positive Nodes

Stage IV Distant Metastatic Disease

There Are Exceptions To The Above Guide!



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ow s pe atr c onco ogy erentfrom adult oncology?

Different Cancers

Few Carcinomas, More Leukemias

Prediliction for Cancer at Unique Ages Growth Spurts

Less Association With Environmental Factors

Cancer is Less Common



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What long term health issues mightsurvivors of cancer have to deal with?

Increased Risk of Second Cancers

,

?Elevated Genetic Risk?

Long-Term Side Effects of Treatment Chemotherapy Heart Failure, Leukemia, Sensory

Neuropathy, Renal Insufficiency, Sterility, Pulmonary

Fibrosis etc.

Radiation Dementia, Sarcomas, Leukemia, GrowthRetardation, Dry Mouth, Strictures, etc.

urgery ymp e ema, a a sorp on, a n enance o

Stomas, Dyspnea, etc.CC-Pieters & Liebmann Feb 11 2011


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ow can you exp a n erences n t eincidence of cancer around the world?

Different Environmental Exposures

n ec ons

HBV and Hepatoma in Asia

EBV and Burkitts Lymphoma in Africa Diets

Esophageal Cancer Belt Caspian Sea to China

Relatively New in Third World

Local Habits

e e u s

Access to Health Care

Cervical Cancer in Third World CC-Pieters & Liebmann Feb 11 2011


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Final Thoughts

Get a Good Nights Sleep

. ,

abstract idea

Obsess Less Over Trivia

Worry More About Understanding the Concepts


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cancer final review