OBC | New development in the therapy of basal cell carcinoma
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Transcript of OBC | New development in the therapy of basal cell carcinoma
Der „Basalzellenkrebs“
E. Krompecher, 1903
1894
Illustration P.G. Unna Today
Photography W. Neuse
1895
Illustration G. Thibierge
Today
Photography W. Neuse
BASAL CELL CARCINOMA
INCIDENCE
Australia up to 2 % per year
USA White population 407 / 100 000 / year
1 million cases in 2005
Half of all cancers
80 % of all NMSC
Worldwide Increasing incidence
BASAL CELL CARCINOMA
RISK FACTORS
Skin type I – II
Ionising radiation
Burns
As, Tar, Smoking
Immunosuppression
Age > 60
Previous BCC: RR 10x
Gene mutations
Ultraviolet !
BASAL CELL CARCINOMA
AND IONIZING RADIATION
Multiple BCCs 20 yrs after irradiation of Hodgkin´s disease
BASAL CELL CARCINOMA
DISTRIBUTION
Head/Neck 60 %
Nose 14 %
Trunk 30 %
Extremities 10 %
BASAL CELL CARCINOMA
PATHOGENESIS
BCC
Genetic
Predisposition Skin type
DNA
Repair
Immuno-
Suppression
UV
Mutations
Autosomal dominant
Multiple BCCs at young age
Skin, CNS, Skeletal involvement
Predisposition to malignancy
(medulloblastoma)
PTCH germ line mutations
NEVOID BASAL CELL CARCINOMA-
SYNDROME (NBCCS)
Ptch Smoh
Shh
extracellular
intracellular
Gli1/2
Nucleus
HIP
PTCH Gli1/2
Sufuh
THE SONIC HEDGEHOG PATHWAY
CCNB1/D2
FOXM1/FOXE
BCL2
PTCH
Human homolog of the Drosophila - Gene patched
Drosophila: segmental development
Function: Receptor for the hedgehog protein Tumor suppressor
PTCH Mutant Wild type
ANALYSIS OF SHH PATHWAY GENES
IN SPORADIC 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
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 genes
Shh pathway is constitutively activated in all BCCs
PTCH+/- MOUSE MODEL
Model of human NBCCS
Body size increased
Medulloblastomas (15%)
BCCs after repetitive
UVB exposure
Medulloblastoma
UVB induced BCCs
„MOUSE SOLARIUM“
GDC-0449
SMALL MOLECULE SMO-INHIBITOR
von Hoff et al., N Engl J Med 2009
PHOTODYNAMIC THERAPY (PDT)
Topical application of
ALA 20 % (3 - 5 h) PDT with
red light
634 nm
PDD with
Wood-Light
417 nm
PHOTODYNAMIC THERAPY
OF NBCCS
Before therapy After 4x PDT
FLUORESCENCE DIAGNOSIS
Pre-operative determination of tumor margins
And I told him, put some cream on
UV PROTECTION