stand der technik und visionen am beispiel der onkologischen diagnostik
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Stand der Technik und Visionen am Beispiel der onkologischen Diagnostik
Onkologische Diagnostik
„Pathology as the enabler of human research“
Crawford und Tykosinski, 2005 Lab Invest
Onkologische Diagnostik - Pathologie
„Cancer classification has been based primarily on morphological appearance“
Golub et al., 1999 Science
Morphologie - Leitmotiv
Prof. Dr. Axel Niendorf
Singer, Suhrkamp 2002
Bronchialkarzinom – Pathologie - Klassifikation
- Grading
- Typing (WHO)
- Staging (UICC)
Adenokarzinom – Lunge - Typing
Prof. Dr. Axel Niendorf
Plattenepithelkarzinom – Lunge - Typing
Prof. Dr. Axel Niendorf
Kleinzelliges Karzinom – Lunge - Typing
Prof. Dr. Axel Niendorf
Bronchialkarzinom - Heterogenität
– innerhalb einer Gruppe
– innerhalb eines Falles: „45% major heterogeneity“
Roggli et al., 1985 Hum Pathol
Prognose – Bronchialkarzinom - Typing
Prof. Dr. Axel Niendorf
Survival Typing
Survival [years]
121086420
1,0
,8
,6
,4
,2
0,0
SCLC (n=80)
NSCLC (n=432)
(Censored cases)
NSCLC
SCLC
Rhode et al., 2003 Dissertation
Prognose – Bronchialkarzinom - Staging
Prof. Dr. Axel Niendorf
Survival UICC-Staging
11109876543210
1,0
,8
,6
,4
,2
0,0
Survival [years]
Stage IV (n=38)
Stage IIIB (n=61)
Stage IIIA (n=91)
Stage IIB (n=68)
Stage IIA (n=20)
Stage IB (n=58)
Stage IA (n=79)
(censored cases) Rhode et al., 2003 Dissertation
Bronchialkarzinom - Grading
Prof. Dr. Axel Niendorf
G I G III
Onkologische Diagnostik - Vision
- Früherkennung
- Stratifizierung (Risk assessment)
- individualisierte Therapieempfehlung
- Therapiemonitoring
Biomarker - Definition
- Objektiv messbares Merkmal
- Indikator eines biologischen Prozesses
Tumor - Eigenschaften
Prof. Dr. Axel Niendorf
Hanahan et al., 2000 Cell
Figure 1. Acquired Capabilities of CancerWe suggest that most if not all cancers have acquired the same set of functional capabilities during their development, albeit through various mechanistic strategies
Biomarker - Analytik
- RNA
- DNA
- Protein
- funktionell
Biomarker – Molekulares Profil
Prof. Dr. Axel Niendorf
Molekulares Profil – Bronchialkarzinom - Zusammenfassung
- bekannte Klassen matchen
- neue Klassen definieren
- Quelle für neue Biomarker
Komplexes Tumorgewebe
Prof. Dr. Axel Niendorf
Figure 3. Tumors as Complex TissuesThe field of cancer research has largely been guided by a reductionist focus on cancer cells and the genes within them (left panel)—a focus that has produced an extraordinary body of knowledge. Looking forward in time, we believe that important new inroads will come from regarding tumors as complex tissues in which mutant cancer cells have conscripted and subverted normal cell types to serve as active collaborators in their neoplastic agenda (right panel). The interactions between the genetically altered malignant cells and these supporting coconspirators will prove critical to understanding cancer pathogenesis and to the development of novel, effective therapies.
Hanahan et al., 2000 Cell
Molekulares Profil - Präparation
Prof. Dr. Axel Niendorf
Mikrodissektion - Morphologie
Prof. Dr. Axel Niendorf
Tissue Microarray
Prof. Dr. Axel Niendorf
Lakhani und Ashworth, 2001 Nature Reviews Cancer
Biomarker -Tumordatenbank
Prof. Dr. Axel Niendorf
Gewebebank
Tumordatenbank
-autom. Mikroskopie-Bildanalyse-Klinische Metadaten
-Genexpressionen-Proteinexpression
Tumordatenbank - Metaanalyse
Prof. Dr. Axel Niendorf
„WorldKnowledge“
Create novel approaches
in diagnostics
MEDEEAPathology
MetalifeIT
Filter & Extract
Onkologische Diagnostik - Schlussfolgerung
- Material
- Verfahren
- Analyse