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