igor goryanin molecular base of cancer modern concept
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- 1. - ( ) mRNA : - - Proteins - ( ) -
- 2. : , , , Genes mRNA Proteins , , , ,
- 3. - Proteomic image Microarray image
- 4. : () , Proteins - Ovarian pattern http://www.cancer.gov/cancertopics/screening
- 5. () ( , , , ..) (targeted therapy) , -,
- 6.
- 7. : : - -
- 8. : , , , ! 1 2 3 4
- 9. , , , ...
- 10. : (Herceptin, Pertuzumab)
- 11. , ErbB - - / ErbB1 (EGFR) Gefitinib AstraZeneca Small molecule, ATP competitor Erlotinib Genentech, Roche Small molecule, ATP competitor Cetuximab Merck mAbErbB2 (HER2) Trastuzumab Genentech mAb (Herceptin) Pertuzumab Genentech mAbErbB3 (HER3) MM-121 Merrimack mAb Pharmaceuticals
- 12. : - (.) suppression Sensistivity Resistance Signal in vitro
- 13. : -
- 14. PTEN anti-ErbB2 :- Faratian et al, Cancer Res, 2009, 69(16):6713-20
- 15. PTEN anti-ErbB2 : - ()Faratian et al, Cancer Res, 2009, 69(16):6713-20
- 16. - Inhibitor 2 Inhibitor 1
- 17. /
- 18. Backup slides
- 19. ~ 300 : : , , , , : , , , , 490 > 2,6 2008 .. , .. ,.. , 2010
- 20. 23,718.5 ( 476,000 ) 16.5 100000 ( 7.7) 288,047.7 199.9 100000
- 21. : 57,9%, 63% 43%! ! ,
- 22. 20
- 23. -: ( ), Pap-test ( ) : , PSA (prostate specific antigen) - , - -
- 24. , (, , ..)
- 25. ,
- 26.
- 27. - : ... : Lee Hood, Institute for Systems Biology
- 28.
- 29. No cancer Mass spectrometry Proteins Blood sample Proteins Blood Best fit molecular fingerprint sample Cancer Normal marker proteins marker proteins Mass spectrometryCancer
- 30. anti-ErbB2 , : Herceptin ( ) 96% vs 95% , 1 (Piccart-Gebhart et al., 2005) 91% vs 87%, 4 (Romond et al., 2005). , - rbB2+
- 31. : - , -ErbB2 - ( )
- 32. : - (.) suppression Sensistivity Resistance Signal in vitro
- 33. : - (.) suppression Sensistivity Resistance Signal in vitro
- 34. : - (.) suppression Sensistivity Resistance Signal in vitro
- 35. ErbB3/2 -ErbB2
- 36. : - (.) suppression Sensistivity Resistance Signal in vitro
- 37. -Per +Per ErbB2 , A.Sorokin
- 38. : - suppression Sensistivity Resistance Signal in vitro
- 39. 2008 .. , .. ,.. , 2010
- 40. 2008 .. , .. ,.. , 2010
- 41. 2008 .. , .. ,.. , 2010
- 42. Best fit molecular fingerprint Normal Cancer
- 43. Diagnostics can stratify populations by drug response Diagnostic test positive Likely to benefit from Dx+ therapy Tx+ Toxicity test positive Likely to have toxic Dx- response Diagnostic test negative Not likely to benefit from therapySeptember 2010 Confidential 43
- 44. SPECIFIED ABSTRACTED Differential equations Markov chains Bayesian networks mechanisms Boolean/fuzzy logic models Statistical mining(includingmolecularstructure-based influencescomputation) relationships Doug Lauffenburger, MIT
- 45. : 70% 15 ; 59,000 (40.0 / 100,000 )
- 46. Lack of response has enormous costsAspect Numeric2008 Rx spend, US 292 B$ (of 800 B$ WW)Percent Rx not effective 20 90% (average 50%)Adverse events, US ~2,000,000Fatal adverse events, US ~100,000Cost adverse drug events, US Cost 45-135 B$Percent events avoidable 20 35%Percent of care decisions informed by 70%diagnosticsDiagnostics as percent of healthcare 3-4%market http://www.dnapolicy.org/images/issuebriefpdfs/PGx%20IB.pdf Jerel Davis, McKinsey & CoSeptember 2010 Confidential 46