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OBC | New development in the therapy of basal cell carcinoma

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Thomas Ruzicka, LM University of Munich, Germany
New development in the therapy of basal cell carcinoma

http://obc2012.outofthebox.si/

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OBC | New development in the therapy of basal cell carcinoma

  1. 1. Der „Basalzellenkrebs“E. Krompecher, 1903
  2. 2. 1894 TodayIllustration P.G. Unna Photography W. Neuse
  3. 3. 1895 TodayIllustration G. Thibierge Photography W. Neuse
  4. 4. BASAL CELL CARCINOMA INCIDENCEAustralia up to 2 % per yearUSA White population 407 / 100 000 / year 1 million cases in 2005 Half of all cancers 80 % of all NMSCWorldwide Increasing incidence
  5. 5. BASAL CELL CARCINOMA RISK FACTORSSkin type I – IIIonising radiationBurnsAs, Tar, SmokingImmunosuppressionAge > 60Previous BCC: RR 10xGene mutationsUltraviolet !
  6. 6. BASAL CELL CARCINOMA AND IONIZING RADIATIONMultiple BCCs 20 yrs after irradiation of Hodgkin´s disease
  7. 7. BASAL CELL CARCINOMA DISTRIBUTIONHead/Neck 60 % Nose 14 %Trunk 30 %Extremities 10 %
  8. 8. BASAL CELL CARCINOMA PATHOGENESIS UV Immuno- DNASuppression Mutations Repair BCC Genetic Skin type Predisposition
  9. 9. NEVOID BASAL CELL CARCINOMA- SYNDROME (NBCCS)Autosomal dominantMultiple BCCs at young ageSkin, CNS, Skeletal involvementPredisposition to malignancy(medulloblastoma)PTCH germ line mutations
  10. 10. THE SONIC HEDGEHOG PATHWAY Shh extracellular Ptch Smoh intracellular PTCH Gli1/2 HIPSufuh CCNB1/D2 Gli1/2 FOXM1/FOXE Nucleus BCL2
  11. 11. PTCHHuman homolog of the Drosophila - Gene patched Wild type PTCH MutantDrosophila: segmental developmentFunction: Receptor for the hedgehog protein Tumor suppressor
  12. 12. ANALYSIS OF SHH PATHWAY GENES IN SPORADIC BCCs PTCH mutations: 28/42 (67%) SMOH mutations: 4/42 (10%) SUFUH mutations: 2/42 (22%) GLI1/GLI2 overexpression: 42/42 (100%)In 70% of BCCs somatic mutations of Shh genesShh pathway is constitutively activated in all BCCs Wolter et al., Cancer Res 57: 2581-2585, 1997 Reifenberger et al., Cancer Res 58: 1798-1803,1998 Reifenberger et al., Br J Dermatol: 43-51, 2005
  13. 13. PTCH+/- MOUSE MODELModel of human NBCCSBody size increasedMedulloblastomas (15%) MedulloblastomaBCCs after repetitive UVB exposure UVB induced BCCs
  14. 14. „MOUSE SOLARIUM“
  15. 15. GDC-0449SMALL MOLECULE SMO-INHIBITOR
  16. 16. von Hoff et al., N Engl J Med 2009
  17. 17. PHOTODYNAMIC THERAPY (PDT) PDD with Wood-LightTopical application of 417 nm PDT withALA 20 % (3 - 5 h) red light 634 nm
  18. 18. PHOTODYNAMIC THERAPY OF NBCCSBefore therapy After 4x PDT
  19. 19. FLUORESCENCE DIAGNOSISPre-operative determination of tumor margins
  20. 20. And I told him,put some cream on
  21. 21. UV PROTECTION

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