OBJECTIVES. 1. List the major hallmarks of cancer. 2. Relate specific genes/proteins to individual hallmarks

Transcription

1 OBJECTIVES 1. List the major hallmarks of cancer 2. Relate specific genes/proteins to individual hallmarks 3. Explain how hallmarks of cancer lead to cancer development

2 Case Study 60 year old female Previously treated for breast cancer (5 years prior); no recurrence Presents with persistent cough, shortness of breath, famgue X- ray reveals small mass in lep lung Source: A biopsy is performed

3 think- discuss- share A physician meets with this pament. What is the first quesmon she asks about the pament s lifestyle?

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6 brainstorming A pathologist analyzes the biopsy sample. What does she look for?, i.e. What informamon is gained from the analysis of the biopsy?

7 TYPES OF LUNG CANCER

8 Biopsy results indicate that pahent has a metastahc tumor of breast cancer origin in lung. Tumor is a carcinoma.

9 QUESTION What changes occurred to a breast epithelial cell that led to the formahon of a metastahc tumor in the lung? Biopsy results indicate that pahent has a metastahc tumor of breast cancer origin in lung. Tumor is a carcinoma.

10 Douglas Hanahan Robert Weinberg

11 Hanahan and Weinberg (2000) Cell, 100:

12 GROWTH FACTOR (GF) RECEPTOR INTRACELLULAR SIGNALING PATHWAY CELL DIVISION

13 GROWTH FACTOR (GF) RECEPTOR Ras INTRACELLULAR SIGNALING PATHWAY CELL DIVISION

14 RECEPTOR Hyperac(ve Mutant Ras in Cancers Ras INTRACELLULAR SIGNALING PATHWAY CELL DIVISION

15 GROWTH FACTOR (GF) Amplified EGF Receptors in Cancer INTRACELLULAR SIGNALING PATHWAY CELL DIVISION

16 CLASSES OF LUNG ADENOCARCINOMA Ras Source: Cheng, L. et al. (2012) Modern Pathology, 25:

17 TARCEVA A DRUG WHICH TARGETS EGF RECEPTOR IN LUNG CANCER

18 Hanahan and Weinberg (2000) Cell, 100:

19 EUKARYOTIC CELL CYCLE

20 RECEPTOR INTRACELLULAR SIGNALING PATHWAY Rb G 0

21 GROWTH FACTOR (GF) RECEPTOR INTRACELLULAR SIGNALING PATHWAY Modified and Inac(ve Rb Rb- P CELL DIVISION

22 RECEPTOR INTRACELLULAR SIGNALING PATHWAY Rb Inac(ve Mutant Rb in Cancer CELL DIVISION

23 p53 s NORMAL ROLE IS TO INHIBIT CELL DIVISION IN RESPONSE TO CELLULAR STRESSES LIKE DNA DAMAGE

24 TUMOR CELLS LACKING p53 DO NOT ARREST CELL CYCLE Source: Molecular Biology of the Cell, Alberts et al.

25 Hanahan and Weinberg (2000) Cell, 100:

26 APOPTOSIS PROGRAMMED CELL DEATH Source: Molecular Biology of the Cell, Alberts et al.

27 INSULIN- LIKE GROWTH FACTOR (IGF- 1) IGF- 1R Ras INTRACELLULAR SIGNALING PATHWAY CELL SURVIVAL CELL DIVISION

28 INSULIN- LIKE GROWTH FACTOR (IGF- 1) IGF- 1R Ras INTRACELLULAR SIGNALING PATHWAY CELL SURVIVAL CELL DIVISION SOME CANCER CELLS UPREGULATE CELL SURVIVAL PATHWAYS TO EVADE APOPTOSIS

29 Hanahan and Weinberg (2000) Cell, 100:

30 TELOMERES ARE CHROMOSOME ENDS TELOMERES ARE MADE BY TELOMERASE EARLY IN DEVELOPMENT; THEN TELOMERASE ACTIVITY IS NORMALLY TURNED OFF TELOMERES SHORTEN WITH EACH CELL DIVISION, ULTIMATELY LEADING TO SENESCENCE

31 CANCER CELLS REACTIVATE TELOMERASE

32 Biopsy results indicate that pahent has a metastahc tumor of breast cancer origin in lung. Tumor is a carcinoma.

33 Hanahan and Weinberg (2000) Cell, 100:

34 The formahon of new blood vessels from pre- exishng blood vessels.

35 VEGF = Vascular Endothelial Growth Factor

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37 Biopsy results indicate that pahent has a metastahc tumor of breast cancer origin in lung. Tumor is a carcinoma.

38 Hanahan and Weinberg (2000) Cell, 100:

39 PRIMARY BREAST CARCINOMA METASTATIC TUMOR IN LUNG

40 METASTASIS CELLS OF PRIMARY TUMOR REDUCE EXPRESSION OF INTERCELLULAR CONNECTIONS (E- CADHERINS) AND CONNECTIONS TO THE EXTRACELLULAR MATRIX (INTEGRINS) TO ALLOW METASTASIS

41 CANCER DEVELOPMENT IS A MULTI- STEP PROCESS. INDIVIDUAL STEPS CAN OCCUR IS DIFFERENT ORDER. Hanahan and Weinberg (2000) Cell, 100:

42 THE HALLMARKS OF CANCER Ras, EGF Receptor Rb, p53 IGF Telomerase VEGF E- cadherin

43 You should be able to List the major hallmarks of cancer 2. Relate specific genes/proteins to individual hallmarks 3. Explain how hallmarks of cancer lead to cancer development