KULIAH KANKER

8/12/2019 KULIAH KANKER

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KankerKuliah Umum

Aru W. Sudoyo


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Besarnya Masalah


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Penyebab Kematian Utama di Dunia

Percent of Total Deaths

US data/Adapted from Cancer Journal for Clinicians , 1994.

33.5%

23.5%

6.7%4.3% 4.0% 3.7%

2.2%1.4% 1.2% 1.2%1.2%


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0 1 2 3 4 5 6 7 8

Tuberculosis

HIV/AIDS

Malaria

Total TB+HIV+Mal

Cancer

Global mortality 2002

WHO, 2003

Millions of deaths


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5

Angka Kematian akibat Kanker : Distribusi Negara Maju danSedang Berkembang

http://www.who.int/healthinfo/statistics/

7.59.1

11.4

Proyeksi WHO di Seluruh Dunia

2.1 2.3 2.5

5.5 6.7 8.9

0 2 4 6 8

10 12

2005 2015 2030 T o

t a l K e m a t

i a n

( d a l a m

j u t a )

Negara-Negara Maju Negara-Negara Sedang Berkembang


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WHO, 2003

Proyeksi Kasus-kasus Kanker Baru per Tahun: Antara Negara Maju dan Berkembang

3

4

5

6

7

8

9

10

1990 1995 2000 2005 2010 2015 2020

n e

w c a n c e r c a s e s ( m

i l l i o n s

)

year

developing

countries

industrializedcountries

NegaraBerkembang

Negara Maju

Tahun


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Kanker Paling Sering( Pathology Based Cancer Registry )

242923%

218121%

99310%

9239%

9159%

7737%

6106%

5595%

5075%

4775%

Cases

Cervix

Breast

Nasopharynx

Rectum

Skin

Ovarium

Thyroid

Colon

Lymphnode


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687

19%

47713%

47613%464

13%

3259%

323

9%

2908%

2457%

1895%

1634%

Cases

Nasopharynx

Prostate

RectumSkin

Lymphnode

Bladder

Colon

Soft Tissue

Nasal Cavity

Thyroid

Kanker Paling Sering Pada Laki-lakiPathology Based Cancer Registry


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MUTASI BERULANG SEBAGAI PENYEBAB KANKER

Sel normal

Mutasipertama

Mutasikedua

Mutasikeempat

Mutasiketiga

Sel-sel

ganas


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Sel normal

Mutasipertama

Mutasikedua

Mutasikeempat

Mutasiketiga

Sel-sel

ganas


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Sel normal

Mutasipertama

Mutasikedua

Mutasikeempat

Mutasiketiga

Sel-sel

ganas


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Sel normal

Mutasipertama

Mutasikedua

Mutasikeempat

Mutasiketiga

Sel-sel

ganas


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Sel normal

Mutasipertama

Mutasikedua

Mutasikeempat

Mutasiketiga

Sel-sel

ganas


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Karsinoma (sel2 yangmelapisi permukaan tubuhdalam dan luar)

Jenis Kanker

paru

Payudara

Ususbesar

Kdg kemihProstat(laki2)

Leukemia(sel-sel darah)Limfoma

(kelenjar dan jaringan limfe)

Sarkoma

Sel-s el otot dan

jairngan penunjang


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Faktor-Faktor Risiko


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ROKOK

- Kanker paru-paru

- Kanker mulut (tembakaukunyah)

- Kanker larynx, pharynx,esophagus (pipa) dan kolon

- Fakta: 514000 kematian karenakanker 164000 disebabkan olehrokok.


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Penyebab Punahnya Dinosaurus


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Kurang berolah raga


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Kegemukan (obesitas)


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Makanan

Rokok : palingpreventable

Makanan : TOTAL >merokok

Makanan : lebih sulitdicegah

Amat terkait dengankebiasaan dan PILIHANbahan-bahan


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9/25/01 Nutrition 28

Peran Faktor Makanan pada

Karsinogenesis

Manifestasi kanker

Struktur DNA

Reaksi dgn sasaran2 dlm selKerusakan DNA, Mutagenesis

Penghambat aktivasi

Blocking Agents

zat penekan

Pajanan thdpKarsinogen


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HETEROCYCLIC AMINES-Memasak daging temperatur/suhutinggi zat kimia (heterocyclicamines/HCAs)

-Perhatikan:- Cara memasak- Temperatur/suhu- Waktu

-HCAs masakan rumah dan nonfast food rest


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Makanan Tinggi Lemak

Asam empedu tinggi + kurang serat

Kotoran lambat Asam empedu

merusak

Jaringan tumbuh takterkontrol Kanker usus besar


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AKRILAMID- Bahan kimia dalam bentuk

butiran kristal atau cairan yangbanyak digunakan padapembuatan kertas, dyes danplastik atau sebagai pada

proses pengolahan air minumdan sampah.

- Efek: kerusakan pada inti sel

- Pembentukan:menggoreng/membakar/merebus pada temperatur tinggi FRENCH FRIES


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Formalin danKankerFormaldehyde has beenclassified as a humancarcinogen (cancer-causingsubstance) by theInternationa l Agenc y forResearch on Cancer and asa probable humancarcinogen by the U.S.Environmental ProtectionAgency Association betweenformaldehyde expo sure

and can cers of the na sal sinuses, nasopharynx , andbrain, an d possiblyleukemia
http://www.cancer.gov/Common/PopUps/popDefinition.aspx?term=cancer&version=Patient&language=Englishhttp://www.cancer.gov/Common/PopUps/popDefinition.aspx?term=cancer&version=Patient&language=Englishhttp://www.cancer.gov/Common/PopUps/popDefinition.aspx?term=carcinogen&version=Patient&language=Englishhttp://www.cancer.gov/Common/PopUps/popDefinition.aspx?term=carcinogen&version=Patient&language=Englishhttp://www.cancer.gov/Common/PopUps/popDefinition.aspx?term=nasal&version=Patient&language=Englishhttp://www.cancer.gov/Common/PopUps/popDefinition.aspx?term=nasopharynx&version=Patient&language=Englishhttp://www.cancer.gov/Common/PopUps/popDefinition.aspx?term=nasopharynx&version=Patient&language=Englishhttp://www.cancer.gov/Common/PopUps/popDefinition.aspx?term=nasal&version=Patient&language=Englishhttp://www.cancer.gov/Common/PopUps/popDefinition.aspx?term=nasopharynx&version=Patient&language=Englishhttp://www.cancer.gov/Common/PopUps/popDefinition.aspx?term=leukemia&version=Patient&language=Englishhttp://www.cancer.gov/Common/PopUps/popDefinition.aspx?term=leukemia&version=Patient&language=Englishhttp://sexychef.blogsome.com/images/baso.jpghttp://www.cancer.gov/Common/PopUps/popDefinition.aspx?term=leukemia&version=Patient&language=Englishhttp://www.cancer.gov/Common/PopUps/popDefinition.aspx?term=nasopharynx&version=Patient&language=Englishhttp://www.cancer.gov/Common/PopUps/popDefinition.aspx?term=nasal&version=Patient&language=Englishhttp://www.cancer.gov/Common/PopUps/popDefinition.aspx?term=carcinogen&version=Patient&language=Englishhttp://www.cancer.gov/Common/PopUps/popDefinition.aspx?term=cancer&version=Patient&language=English


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Nutrition 33

Proportion of Cancer DeathsAttributable to Various Factors

(Doll and Peto, 1981)Factor Best Estimate Range of Acceptable Estimates

Tobacco 30 25-40

Alcohol 3 2-4

Diet 35 10-70Food Additives 1 (-5**)-2

Reproductive/Sexual Behavior 7 1-13

Occupation 4 2-8

Pollution 2 1-5

Industrial Products 1 1-2

Medicines/Medical Products 1 0.5-3

Geophysical Factors 3 2-4

Infection 10 1-?


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Faktor-Faktor Makanan yang berhubungan

dengan Pengurangan Risiko Kanker Dietary fiber

colorectal, pancreas, breast

Folic acid cervix, colorectal

Vitamin D and calcium colorectal, breast

Antioxidants (nutrient and non-

nutrient) from foods colorectal, lung, breast, cervix,

prostate, esophagus, stomach

Vitamin C from foods oral cavity, esophagus, lung,

stomach, pancreas, cervix

Tea (flavonoids) lung, colorectal

Alpha-tocopherol lung

Soy isoflavones? breast


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Nutrition

Faktor makanan yang memicu /meningkatkan risiko Kanker

Alcohol mouth, pharnyx, larnyx,

esophagus, liver-convincing

breast, colon, rectum-probable

Salt stomach- probable

Sucrose colon, rectum

Meat (especially charbroiled) colon and rectum- probable

Total and Saturated Fat lung, colon, rectum, breast,

prostate- possible


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9/25/01 Nutrition 36

Chemopreventive Non-nutritive

Dietary FactorsCompound Food Source

Cinnamic acid Fruit, vegetables, coffee beans

Flavonoids (catechins,quercitin, isoflavones,anthocyanins)

vegetables, fruit, citrus fruit, celery,parsley,onions, grains, tea, soybean

Indoles Cruciferous vegetables

Isothiocyanates Cruciferous vegetables

Lignans Whole grains, flax

Organosulfur Garlic, Onion

Terpenes Citrus, spices


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Metastasis


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Metastasis Terjadi pada setiap jenis kanker Penyebaran Jauh ke organ tubuh lainnya

Paru Hati

Buli-buli Rongga abdomen Dapat terjadi setelah ada kesembuhan (remisi)

Paling tinggi dalam dua tahun pertama

Semakin kecil di tahun-tahun selanjutnya


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Modalitas (cara) pengobatan lain:pada kanker dengan penyebaran

(metastasis)

Paling banyak: terapi regional / lokal TACE Radiofrequency ablation (untuk metastasis

hati) Bedah dingin / cryosurgery

Belum baku / standar Biasanya PALIATIF bukan KURATIF


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Pengobatan


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Apakah bisa disembuhkan ?


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KematianAlami

Lahir

kerentananPre-initiation

Perubahanmenjadi ganas

Evolusi ?progresi

Fenotipmematikan

Rentang Usia

Kematiankrn Kanker

Beban Kanker

Proses Kanker


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KematianAlami

Lahir Rentang Usia

KematianakibatKanker

Cegah atau

Perlambat

Deteks i d anEradikasi

Ku asai Kanker

2010 2020

Kesempatan untuk Intervensi


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KematianAlami

Lahir

kerentananPre-initiation

Perubahanmenjadi ganas

Evolusi ?progresi

Fenotipmematikan

Rentang Usia

Kematiankrn Kanker

Beban Kanker

Proses Kanker


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KematianAlami

Lahir Rentang Usia


Cegah atau

Perlambat


Ku asai Kanker

2012 2022



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KematianAlami

Lahir Rentang Usia


Cegah atau

Perlambat


Ku asai Kanker

2012 2022



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Kemoterapi


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Cytotoxic Chemotherapy

Cytotoxic literally translated means toxic tocells. Hence these drugs are those which killcells.

Chemotherapy - the treatment of disease by theuse of chemical substances


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History of Cancer Chemotherapy

1940-1950 Beginnings of the modern era of chemotherapy

traced directly to discovery of nitrogen

mustard (chemical warfare agent) as aneffective treatment for cancer.

Autopsy observations of people exposed tomustard gas revealed lymphoid and myeloidsuppression


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Cl

S

Cl

R

NCl Cl

Chemical Warfare circa 1914

Two most common agents: Chlorine gas Mustard gas

Mustard Gas!

Nitrogen Mustard


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1940-1950 Goodman and Gilman reasoned that this agent

could be used to treat lymphoma, since

lymphoma is a tumour of lymphoid cells. Set up an animal model, establishing

lymphoma in mice and treated them withmustard gas.


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1940-1950 In collaboration with a thoracic surgeon, they injected

a related agent (mustine) into a patient with non-

hodgkins lymphoma and observed a dramaticreduction in the patients tumour mass.

Although this effect only lasted a few weeks, this wasthe first step to the realisation that cancer could betreated with pharmacological agents


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Combination chemotherapy 1965 Cancer cells could conceivably mutate to

become resistant to a single agent, but using

different drugs concurrently would make itextremely difficult for the tumour to developresistance to the combination.

Induced long term remission in children withALL.


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BASIC PRINCIPLES

Prevents cancer cells from multiplying,invading, metastasising and killing patient.

Affects cell multiplication and tumour growth. Especially affects cells with a rapid rate of

turnover. Effectively given - marked effect and minimal

toxicity.


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CELL CYCLE


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ROUTES OF ADMINISTRATION

Orally e.g. methotrexate

IV

SC

Intrathecal e.g. methotrexate, cytarabine

CELL CYCLE SPECIFIC VERSUS NON


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CELL CYCLE SPECIFIC VERSUS NON-SPECIFIC

Certain chemotherapy drugs require cells to bein cycle for activity (i.e. not resting).

Cell Cycle specific - most active against cellsin a specific phase therefore need prolongedexposure or repeated doses.

Cell Cycle Non-specific - most effectiveagainst actively dividing cells but alsoeffective in G0.


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BASIC PRINCIPLES

Prevents cancer cells from multiplying,invading, metastasising and killing patient.

Affects cell multiplication and tumour growth. Especially affects cells with a rapid rate of

turnover. Effectively given - marked effect and minimal

toxicity.

Significant Progress has Already


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64

Significant Progress has Alreadybeen Achieved in Extending Life

64

12 mo

15-17 mo

23+ mo

2000s

1980s

Anthracyclines

BSC

Taxanes (Docetaxel, Paclitaxel)

1990s

Metastatic Breast Cancer(Median Overall Survival - months)

6 mo

10-12 mo

18-22+ mo

2000s

1980s

5-FU/LV

+Oxaliplatin/ Irinotecan/bevacizumab

1990s

BSC

Metastatic Colorectal Cancer(Median Overall Survival - months)

BSC Best Supportive Care


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Sasaran KemoterapiSembuh : tumor atau kanker hilang dan tidakkembali lagi

Kontrol : bila sembuh tidak mungkin, tujuannyaadalah untuk menghentikan penyakit (kanker tidaktumbuh dan menyebar lagi), perpanjang hidupdengan kualitas hidup terbaik

Paliasi : bila kontrol tidak mungkin atau kankersudah stadium lanjut. Kemoterapi bertujuanmengurangi gejala dan mempertahankan kualitashidup yang baik


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Bagaimana kerja kemoterapi?

Menyerang sel-selyang sedangmembelah cepatMenghambat sel yangsedang membelah


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Bagaimana kerja kemoterapi?

Karena itu :digunakan

KOMBINASI OBAT-OBATAN (multipledrugs)

DiberikanBEBERAPA KALI


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Tumor growth kinetics


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CLASSIFICATION OF CYTOTOXIC AGENTS

BUSULFAN CYTOSINE ETOPOSIDE BLEOMYCIN L-ASPARAGINASE

CARMUSTINE ARABINOSIDE TENIPOSIDE DACTINOMYCIN HYDROXYUREA

CHLORAMBUCIL FLOXURIDINE VINBLASTINE DAUNORUBICIN PROCARBAZINE

CISPLATIN FLUOROURACIL VINCRISTINE DOXORUBICIN

CYCLOPHOSPHAMIDE MERCAPTOPURINE VINDESINE MITOMYCIN-C

IFOSFAMIDE METHOTREXATE TAXOIDS MITOXANTRONE

MELPHALAN PLICAMYCIN

ALKYLATINGAGENTS

ANTI-METABOLITES

MITOTICINHIBITORS

ANTIBIOTICS OTHERS


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Rand 50.3

Drug Targets in Cancer Chemotherapy


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Drug Targets in Cancer Chemotherapy1. DNA

a) bondage --alkylating agents (mechlorethamine, cyclophosphamide), cisplatin

b) vaporization --bleomycin

c) confusion --actinomycin D, doxorubicin, etoposide,irinotecan

d) starvation --methotrexate, 6-thioguanine,5-fluorouracil, cytosine arabinoside,hydroxyurea

e) regulation --tamoxifen, aromatase inhibitors

2. Protein synthesis: L-asparaginase

3. Mitotic Apparatus: vincristine, vinblastine, paclitaxel

4. Specific antigens: therapeutic antibodies (e.g. Herceptin, Avastin)

5. Protein kinase inhibitors: Gleevec (imatinib) inhibits BCR-ABL which causes

CML(chronic myeloid leukemia)


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How to Target Cancer Cells?

Exploit properties unique to Cancer cellsThe Grow th Facto r (Fract io n)

Major determinant of chemotherapy effectivenessDefined: Proliferating:Resting cell ratioRelated to the Cell Cycle

Enzyme productionVascularization

h C ll C l ( fl hb k )


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The Cell Cycle ( flashback )


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Drug Targets

Chemotherapy drugs are more toxic to tissue withhigh grow th f rac t ionHigh fraction = rapidly growing

Disseminated cancersLow fraction = slow growing

Solid tumors


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Obstacles to Chemotherapy

Healthy High Growth Fraction AreasBone marrowSkinHair follicles

SpermGastrointestinal tract

Toxicity is Dose LimitingPoor selectivity of drugsHealthy and cancerous cells affected

Toxicity Roadmap handout


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Toxicity Roadmap - handout


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Major Toxicities

Bone Marrow SuppressionNeutropenia Low WBCG-CSF ( filgrastim ) & GM-CSF ( sargramostim )

Thrombocytopenia Low platelete countOprelvekin ( Neumega )

Anemia Low RBChttp://www.medscape.com/mp/rc/anemiaErythropoetin

Digestive Tract ProblemsStomatitis inflammation of oral mucosaDiarrhea impaired nutrient absorption

Nausea & Vomiting (N/V)Occurs 17 98% (Psych factors)Ondansetron ( Zofran ) and others (handout)


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Major Toxicities cont

Other Alopecia hair lossReproductive sterility in malesHyperuricemia increased urination (DNA)Extravasation of vesicantsDrug-specific (hepatic, coronary, etc)Carcinogenesis some patients sensitive


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Obstacles cont

Cure requires 100% cancer cell deathNearly impossible!

Kinetic problems (drugs are 1 st order)Nonparticipation of immune system

Treatment duration? Example

Patient has 10 12 cancer cells systemicallyTreatment kills 99.999%Patient still has 10 7 cancer cells

Ob l D i P i


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Obstacles:Detection vs. Prognosis


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Absence of Early Detection

Only cervical cancer is detectable earlyConsequences of late detection

MetastasesDecreased responsiveness to Chemo

Solid tumors respond poorlyDrug resistanceTumor Cell HeterogeneityLimited Access (diffusion, transport, etc.)

Patient debilitation


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Resistance Mechanisms

Often produced by the drug itself (mutagen)Cellular adaptation altered enzyme levelsExample: Methotrexate increased dihydrofolatereductase produced to overwhelm drug

Reduced drug transport into cells

Reduced molecular target affinityStimulation of alternative biosynthetic pathwaysImpaired activation or increased metabolismCellular repair mechanisms for DNA

Example: repair of crosslinks or scission caused by

alkylating agentsMultiple Drug Resistance P-glycoproteinDrug efflux pumps become overexpressed


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Resistance cont


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Multidrug Resistance

Due to Increased expression of pumps Affected Drugs

AntibioticsVinca alkaloids

Surprising cross-resistance!No common mechanism of action!


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Chemo Strategies

Intermittent chemotherapyCombination chemotherapyRegional drug delivery

Intra-arterial solid tumorsIntrathecal CNS delivery (non-BBB drugs)Intracavity pleural, peritoneal, bladderPortal Vein Liver

Brain Implants


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Chemo Strategies cont

Intermittent Chemotherapy


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Cytotoxic Drugs

Classes

Alkylating agents Antimetabolites Antitumor antibioticsMitotic inhibitorsTopoisomerase inhibitorsOther


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Cell Cycle Specific Drugs

Toxic to cells in a specific phaseVincristine - causes mitotic arrestOnly effective in M-Phase

Require long presenceProlonged infusionsMultiple doses

Known as Schedule Dependent DrugsClasses

Antimetabolites (S)

Mitotic Inhibitors (M) Asparaginase (G 1 & S)Bleomycin (G 2)Etoposide (G 2)


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The Cell Cycle ( flashback )


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Cell Cycle Nonspecific Drugs

Act during any phase (even G 0)Synergistic w/cell cycle specific drugsMore toxic to proliferating cells

Cells use G 0 for repairToxicity apparent during proliferation

Include Alkylating Agents

Most antitumor antibiotics


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Cara Pemberian Kemoterapi

Oral (tablet)Parenteral (infus)

Intravena (perifer)Kateter sentral

Regional


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Kemoterapi Oral

Obat minumTidak banyak jenisnyaEfek samping samaLebih praktis
http://www.uschemist.com/pcat-gifs/products-small/cancer-bg2.jpg


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Vena perifer


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Kateter Sentral

Lengan bebas daritusukan

Aman dari infeksiPermanen


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Setelah 2004 ..

Pengetahuan mengenai perangai sel kanker >>Diketahui adanya reseptor -reseptor khususpada permukaan sel yang mempengaruhipertumbuhan

Mulai ditemukan berbagai obat yangmentargetkan reseptor2 tersebut targeted therapi atau obat target

Tempat Pemberian


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p


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Kemoterapi Intratekal


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Kemoterapi Regional

Obat Sitostatika Alkohol PekatRadioFrequency

AblationLokal


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Terapi Innovatif

f h h


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Target Therapy: Obat Pintar?

Smart Bomb


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Ob T / T d Th


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Obat Target / Targeted Therapy

Memberi tambahan harapan hidup (survival)Ditambahkan pada obat utama Sitostatik ?Kemotrapi + Terapi Target

Tetap tidak bisa menggantikan kemoterapiEfek samping : lebih sedikitKesulitannya : TARGET YANG MANA

clinicaloptions.com/oncologyTruth and Consequences: Antiangiogenic Therapies in Cancer


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Peran Terapi Biologik



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Proliferation MetastasisAngiogenesisApoptosis

Shc

PI3-K

RafMEKK-1

MEKMKK-7

JNKERK

Ras

mTOR

Grb2

AKT

Sos-1

Sasaran yg mana?



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Shc

PI3-K

RafMEKK-1

MEKMKK-7

JNK ERK

Ras

mTOR

Grb2

AKT

Sos-1

Sasaran yg mana ?



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Courtesy of I. Serebriiskii and E. Golemis, Fox Chase Cancer Center.

Sos-1

Ras

MEKK-1MEK

Shc

PI3-K

Raf

MKK-7

Grb2

AKT

JNK

ERK



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Courtesy of I. Serebriiskii and E. Golemis, Fox Chase Cancer Center.

Sos-1

Ras

MEKK-1MEK

Shc

PI3-K

Raf

MKK-7

Grb2

AKT

JNK

ERK


The Family of VEGF and VEGFRs


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The Family of VEGF and VEGFRsEpigenetic Induction

Hypoxia, cytokines, sex hormones,growth factors, chemokines

Genetic Induction

Mutant p53 , VHL, PTEN-suppressor genes, and activatedoncogenes (eg, ras, src, EGFR, and erb B-2/HER2 )

VEGF-A 121 VEGF-A 165VEGF-B PIGF

VEGF-CVEGF-D

s s s s Plasma

membrane

Endothelial

cell

VEGFR-1(flt-1)

NRP-1 NRP-2 VEGFR-3

(flt-4)

VEGFR-2(flk-1/KDR)

HostVEGF

Vascularpermeability Proliferation

Survival Migration

Mobilization(eg, of VEGFR-2+ endothelialprogenitor cells)

PLC g

Raf

MEK

MAPK

PKC PI3K

AKT

Kerbel RS. N Engl J Med. 2008;358:2039-2049.Copyright 2008 Massachusetts Medical Society. All rights reserved.


A i i i i l d th h t t f ti


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Angiogenesis is involved throughout tumour formation,growth and metastasis

Adapted from Poon RT, et al. J Clin Oncol 2001;19:1207 25

Stages at which angiogenesis plays a role in tumour progression

Premalignantstage

Malignanttumour

Tumourgrowth

Vascularinvasion

Dormantmicrometastasis

Overtmetastasis

(Avasculartumour)

(Angiogenicswitch)

(Vascularisedtumour)

(Tumour cellintravasation)

(Seeding indistant organs)

(Secondaryangiogenesis)



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The VEGF Family and Its Receptors

Neufeld G, et al. FASEB J. 1999;13:9-22.

VEGFR-3(Flt-4)

VEGFR-2(Flk-1/KDR)

VEGFR-1(Flt-1)

Angiogenesis LymphangiogenesisAngiogenesis

Lymphangiogenesis

PIGF VEGF-A VEGF-B VEGF-C VEGF-D

VEGF regulates angiogenesis via interaction with receptor tyrosine kinases

VEGFR-2/KDR and VEGFR-1/Flt-1



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ProliferationApoptosis Resistance Transcription

TGF Interleukin-8bFGF VEGF

MetastasisAngiogenesis

Shc

PI3K

RafMEKK-1

MEKMKK-7

JNK ERK

Ras

mTOR

Grb2

AKT

Sos-1

EGF Pathway

Jalur pensinyalan estrogen


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Jalur pensinyalan estrogen

Osborne CK, Schiff R. Annu. Rev. Med. 2011 62: 233-47.

The HER2 signaling pathway


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The HER2 signaling pathway

ER

Nucleus

c-myc

Raf

MEK 1/2

MAPK

Akt

GSK3 BAD

Cell-cycleprogression

PTEN

mTOR

p27

Cyclin D1, E

FKHR

Grb2 Sos

Cell survival

Ras

Shc SosGrb2

PI3K

Cell proliferation

HER ligandsNK cell

FcGR

ER

p95 HER2

HER1 HER2 HER3 IGF1RHER2

Courtesy of L Gianni

Jalur pensinyalan HER2:b


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sasaran obat

ER

Nucleus

c-myc

Raf

MEK 1/2

MAPK

Akt

GSK3 BAD

Cell-cycleprogression

PTEN

mTOR

p27

Cyclin D1, E

FKHR

Grb2 Sos

Cell survival

Ras

Shc SosGrb2

PI3K

Cell proliferation

HER ligandsNK cell

FcGR

ER

p95 HER2

HER1 HER2 HER3 IGF1RHER2


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Tantangan di Masa Depan:

perangai kankersebagai target


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Personalized Medicine :B i C t


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Basic Concept


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TERIMA KASIH ATASPERHATIANNYA


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Documents

KULIAH KANKER