National R&D Oncology ConsortiumPI: J. Tímár MD PhD

National Institute of OncologyRath Gy 7-9, Budapest,H-1122 Hungary

Cancer morbidity and mortality’1999, HungaryCancer morbidity and mortality’1999, Hungary

1. breast 1. breast 1. lung 1. lung2. colorectal 2. colorectal 2. colorectal 2. colorectal3. lung 3. lung 3. head and neck 3. head and neck4. stomach 4. skin 4. prostate 4. prostate5. pancreas 5. cervix 5. stomach 5. skin6. leukemia 6. uterus 6. pancreas 6. bladder7. ovary 7. stomach 7. leukemia 7. stomach8. cervix 8. ovary 8. bladder 8. kidney9. liver 9. leukemia 9. liver 9. leukemia10.uterus 10.pancreas 10.kidney 10.pancreas

1. breast 1. breast 1. lung 1. lung2. colorectal 2. colorectal 2. colorectal 2. colorectal3. lung 3. lung 3. head and neck 3. head and neck4. stomach 4. skin 4. prostate 4. prostate5. pancreas 5. cervix 5. stomach 5. skin6. leukemia 6. uterus 6. pancreas 6. bladder7. ovary 7. stomach 7. leukemia 7. stomach8. cervix 8. ovary 8. bladder 8. kidney9. liver 9. leukemia 9. liver 9. leukemia10.uterus 10.pancreas 10.kidney 10.pancreas

femalefemale malemalefemalefemale malemale

MT (15000) MB MT (19000) MB MT (15000) MB MT (19000) MB

National Oncology R&D Conzorcium (Hungary)

National Oncology R&D Conzorcium (Hungary)

• National Institute of Neurosurgery• National Institute of Pulmonology• National Institute of Epidemiology• Department of Pediatrics, Debrecen U.• Department of Immunology and

Biotechnology, Pécs University• 1st Institute of Pathology & Experimental

Cancer Research, Semmelweis University, Budapest

• National Institute of Neurosurgery• National Institute of Pulmonology• National Institute of Epidemiology• Department of Pediatrics, Debrecen U.• Department of Immunology and

Biotechnology, Pécs University• 1st Institute of Pathology & Experimental

Cancer Research, Semmelweis University, Budapest

• Department of Oncotherapy, Szeged University

• Institute of Biotechnology, Bay Z. Fundation, Szeged

• National Institute of Rabiobiology• AstraZeneca Hungary• Aventis Pharma Hungary• Béres Co. Hungary• Byk-Gulden• Janssen-Cilag, Johnson and Johnson• Pannonpark Ltd• Pharmacia Hungary• Bristol-Myers-Squibb Hungary

• Department of Oncotherapy, Szeged University

• Institute of Biotechnology, Bay Z. Fundation, Szeged

• National Institute of Rabiobiology• AstraZeneca Hungary• Aventis Pharma Hungary• Béres Co. Hungary• Byk-Gulden• Janssen-Cilag, Johnson and Johnson• Pannonpark Ltd• Pharmacia Hungary• Bristol-Myers-Squibb Hungary

National institute of Oncology

Cancer types to be investigatedCancer types to be investigated• Breast ca.• Lung ca.• Colorectal ca.• Head and neck ca.• Cervical ca.• Ovarian ca.• Malignant melanoma• Soft tissue sarcoma• Pediatric cancers: acute leukemia

neuroblastomanephroblastoma

• glioblastoma

• Breast ca.• Lung ca.• Colorectal ca.• Head and neck ca.• Cervical ca.• Ovarian ca.• Malignant melanoma• Soft tissue sarcoma• Pediatric cancers: acute leukemia

neuroblastomanephroblastoma

• glioblastoma

MethodologyMethodology• Laser-microdissection• Global genome analysis• DNA microarry design, production• real time quantitatív PCR• antibody design and production• protein-chip technology• in situ hibridization

• Laser-microdissection• Global genome analysis• DNA microarry design, production• real time quantitatív PCR• antibody design and production• protein-chip technology• in situ hibridization

Laser-microdissectionLaser-microdissection

DNSDNS

proteinprotein

RNSRNS

Breast cancer

T V NGAPDH

MAM

HER-2

TOPT II

Mutational analysis

10x20x40x80x160x2 kópia1 kópia

Quantitative PCR

Confocal Laser scanning microscopy

Screening and preventionScreening and prevention

• Susceptibility:

drug metabolizing enzim-polymorphism

• Familiar breast, ovarian and colorectal cancer screening

• Genetical predisposition

• Neuroblastoma

• Susceptibility:

drug metabolizing enzim-polymorphism

• Familiar breast, ovarian and colorectal cancer screening

• Genetical predisposition

• Neuroblastoma

DiagnosticsDiagnostics• Molecular diagnostics soft tissue tumors• Molecular staging colorectal-, breast-, head and neck, ALL, NBL• Prognostic pathology

colorectal-, breast-, lung-,head and neck, melanoma

• Sensitivity to therapy:drug metabolizing enzime polymorphismdrug-target identification

• Molecular diagnostics soft tissue tumors• Molecular staging colorectal-, breast-, head and neck, ALL, NBL• Prognostic pathology

colorectal-, breast-, lung-,head and neck, melanoma

• Sensitivity to therapy:drug metabolizing enzime polymorphismdrug-target identification

Novel therapeutic modalitiesNovel therapeutic modalities• Breast cancer:

Chemoprevention, New taxanescombination of taxanes and Herceptin

• Melanoma:Fragmin (lmw heparin)

• Cervical ca., rectal ca:rhErythropoetin

• Glioblastoma:gene therapy

• Breast cancer:Chemoprevention, New taxanescombination of taxanes and Herceptin

• Melanoma:Fragmin (lmw heparin)

• Cervical ca., rectal ca:rhErythropoetin

• Glioblastoma:gene therapy

Biotech products• New method for blood detection in the stool• WT1 oncogene probes, antibodies• “Designer” oligo-chips for

differential diagnosis of soft tissue tumorsdrug targets in breast-, head and neck cancersGene-map of tumor progressiondrig metabolizing enzime polymorphism

• Design of protein chips for tumor progression• cytokine-producing vestor systems• geneticaly engenered human glioblastoma cell lines

• New method for blood detection in the stool• WT1 oncogene probes, antibodies• “Designer” oligo-chips for

differential diagnosis of soft tissue tumorsdrug targets in breast-, head and neck cancersGene-map of tumor progressiondrig metabolizing enzime polymorphism

• Design of protein chips for tumor progression• cytokine-producing vestor systems• geneticaly engenered human glioblastoma cell lines

1.Mol - epidemiol1.Mol - epidemiol1.Mol - epidemiol1.Mol - epidemiol

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2.Screening and prognosis2.Screening and prognosisof colorectal cancerof colorectal cancer2.Screening and prognosis2.Screening and prognosisof colorectal cancerof colorectal cancer

3.Mol3.Moldiagdiagnosnosticstics

3.Mol3.Moldiagdiagnosnosticstics

4. Mol.diag4. Mol.diag..therapy of therapy of breastbreastcccc

4. Mol.diag4. Mol.diag..therapy of therapy of breastbreastcccc

5.Mol.epidemiol. Diag.5.Mol.epidemiol. Diag.of head and neck cancerof head and neck cancer5.Mol.epidemiol. Diag.5.Mol.epidemiol. Diag.of head and neck cancerof head and neck cancer

9.Gene therapy9.Gene therapyof brain tumorsof brain tumors9.Gene therapy9.Gene therapyof brain tumorsof brain tumors

6. Pediatric oncology6. Pediatric oncology6. Pediatric oncology6. Pediatric oncology

7.Tumor 7.Tumor ProgressionProgression7.Tumor 7.Tumor ProgressionProgression

8.Molecular8.Molecularpharmacologypharmacology8.Molecular8.Molecularpharmacologypharmacology

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J. Tímár PI