1. 25 2010

2. ?

• , :

• • , , .

• - (Targeted therapy)

• • , ,

3.

4.

• -

5.

• ,

6. (Targeted therapy)

• ,

• ( ), ,

7. -

8. , , Tykerb Trastuzumab ErbB3 ErbB2 ErbB1 ErbB2 Pertuzumab IGF-IR Pazopanib Bevacizumab Ertumaxomab Tanespimycin Alvespimycin Vorinostat Temsirolimus Everolimus Sunitinib HDAC=histone deacetylase VEGF PDGFR VEGFR Vascular endothelial cell membrane PI3K mTOR Akt HSP90 HDAC

9.

• • Herceptin

• • ( Tykerb )

• • TDM1

• • PARP

10.

11. -

• -: ,

• -: , , -

• HER-2 -, - ( Herceptin)

• -: HER -2 , ,

12. HER-2

• ~ 20% HER-2

13. HER

14. HER-2 ,

15. ?

16. R-2 Herceptin HER-2 , ,

17. Herceptin

18. Herceptin H R-2

19. HERCEPTIN

• Herceptin , , ,

20. HERCEPTIN

• Herceptin ,

21. HERCEPTIN , 52% 46% 40%

22. Herceptin: 10- Weisgerber-Kriegl et al. ASCO 2008 abstract 6589

23. HERCEPTIN HER-2

• -

• - , , ( beyond progression)

24. HERCEPTIN HER-2

25. R-2 ( Tykerb) HER -2 ,

26. - , Ligands HER-2 Other ErbB PI3K/Akt pathway MAPK pathway (Ras/Raf/ MEK/ERK) PI3K/Akt pathway MAPK pathway (Ras/Raf/ MEK/ERK)

27. , ( Tykerb)

• HER-2 -

• - , HER-2 , HER-2 , Herceptin

28.

• - :

29.

30.

• Herceptin, ( )

31.

• + , 2007 ( FDA)

• 2010

32. ,

33. - () ( VEGF) EGF IGF-1 PDGF IL-8 bFGF COX-2 NO VEGF H 2 O 2 P P P P IGF = insulin-like growth factor PDGF = platelet-derived growth factor

34. VEGF -

• • VEGF ,

35. ?

• ( VEGF) -

36. , ( VEGF)

• -,

VEGF

37. ( VEGF) -

38. 1 2 3 1 2 3 1 . Willett et, al. Nat Med 2004; 2 . Baluk, et al. Curr Opin Genet Dev 2005; 3 . Inai, et al. Am J Pathol 2004; 4 . Gerber, et al. Cancer Res 2005; 5 . Jain. Science 2005

39.

• , , ,

40.

• : , ,

• (beyond progression)

• ,

41.

42.

• ,

• , ,

43.

44. HER-2

• - DM1 Herceptin

• TDM1

45. TDM1

• HER-2

• • HER-2

46. PARP

47.

• , - ( BRCA, PARP . )

• ,

48. PARP+ BRCA+

49.

• BRCA1-2

• • ( )

• BRCA - , ( - triple negative)

50. BRCA PARP (1) BRCA PARP++

51. BRCA PARP (2) BRCA PARP++

52. ?

53. PARP

• PARP BRCA ,

54. PARP PARP- BRCA

55. PARP

• ( 2) PARP :

• • BRCA1-2

• • -

56.

• HER-2 .

• Herceptin- HER-2

• HER-2 ()

57.

• - -,

58.

• - ,

59.

• ...

60.