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Lorenzo MAGGI Lorenzo MAGGI 16-12-200616-12-2006 DHO - NOSGDD DHO - NOSGDD
• Associazione con neoplasie ovaio, mammella, colon
• Diabete
• Calcolosi vie biliari
• Ipertensione
TUMORI ENDOMETRIO: FATTORI DI RISCHIO
Tessutali
• Citologici: - numero di ploidia
- cellule in fase S
- anomalie nucleari
- alterazioni geniche/genomiche
• Istologici: - grading, invasione vascolare
- estensione rispetto al miometrio
- estensione a cervice uterina
• Stadiativi: - estensione a lnd, annessi, peritoneo, metastasi
TUMORI ENDOMETRIO
CLASSIFICAZIONE ISTOLOGICA
• Adenocarcinoma endometrioide- a differenziazione squamosa- villoghiandolare- secernente- cellule ciliate
• Adenocarcinoma mucinoso• Adenocarcinoma sieroso• Adenocarcinoma a cellule chiare• Adenocarcinoma di tipo misto• Adenocarcinoma a cellule squamose• Adenocarcinoma a cellule transizionali• Adenocarcinoma a piccole cellule• Adenocarcinoma indifferenziato
75-80%TIPO I
estrogeno-dipendente
TIPO IIestrogeno-indipendente
20-25%
TUMORI ENDOMETRIO
CLASSIFICAZIONE ISTOLOGICA
• Adenocarcinoma endometrioide- a differenziazione squamosa- villoghiandolare- secernente- cellule ciliate
• Adenocarcinoma mucinoso• Adenocarcinoma sieroso• Adenocarcinoma a cellule chiare• Adenocarcinoma di tipo misto• Adenocarcinoma a cellule squamose• Adenocarcinoma a cellule transizionali• Adenocarcinoma a piccole cellule• Adenocarcinoma indifferenziato
CHEMIOTERAPIA O RADIOTERAPIACHEMIOTERAPIA O RADIOTERAPIA
TUMORI ENDOMETRIO
CHEMIOTERAPIA E RADIOTERAPIA: CHEMIOTERAPIA E RADIOTERAPIA: … … UNA O AMBEDUE UNA O AMBEDUE
• ILIADE: Studio Multicentrico Nazionale su:- estensione dell'isterectomia (ILIADE-1) - ruolo della linfadenectomia (ILIADE-2) - la terapia adiuvante (ILIADE-3)
-(TORINO - A.O. REGINA MARGHERITA - S. ANNA)
• RTOG 9905: “A Phase III Study of Adjuvant Postoperative Irradiation With or Without Cisplatin/Paclitaxel Chemotherapy following TAH/BSO for Patients with Endometrial Cancer.
ErbB Family of Tyrosine Kinase ReceptorsErbB Family of Tyrosine Kinase Receptors
Four members:– ErbB-1 (EGFR/HER1)– ErbB-2 (HER2)– ErbB-3 (HER3)– ErbB-4 (HER4)
Extracellular Domain(Binds Ligand)
TMDomain
Cytoplasmic Domain(Kinase Activity)
TUMORI ENDOMETRIO
• • NUOVE TERAPIE • NUOVE TERAPIE •
ErbB Ligand Specificity
ErbB-1 (EGFR)
HER2
ErbB-2
HER2/neu
ErbB-3
HER3
ErbB-4
HER4
EGF ? Heregulin Heregulin
TGF-α (Neuregulin) HB EGF
Amphiregulin Betacellulin
HB EGF Epiregulin
Betacellulin
Epiregulin
Ligand binding
Tyr-Kinase
C-terminus
EC
IC
Lig
and
s
Degradation
Receptorexpression
Ligandbinding
Hetero/homodimerization
TK activationand tyrosine
transphosphorylationSignal
transductionReceptor
internalization
Degradation orreexpression
Clathrin pit
7
1 2 34
6
5
Receptor Activation Process
Survival
Proliferation
Cell-cycle progression
P
P
P
P
P
P
P
P
P
P
P
P
Ligand
Clathrinpit
Degradation orreexpression
ErbB Signaling Pathway
Grb2 Sos
Shc Grb2Sos
PI3KAkt
Ras
Raf
MEK1/2
MAPKBAD
Survival Proliferation
PTEN
mTOR
Cell-cycle progression
FKHRGSK3p27
Cyclin D1, E
OLD AND NEW PERSPECTIVES IN THE PHARMACOLOGICAL TREATMENT OF ADVANCED OR RECURRENT ENDOMETRIAL CANCER: HORMONAL THERAPY, CHEMOTHERAPY AND MOLECULARLY TARGETEDTARGETED THERAPIES Gadducci A. e coll: Critical Reviews in Oncology/Hematology, 2006
… Mammalian target of the rapamycin (mTOR) inhibitors, epidermal growth factor receptor inhibitors (gefitinib, erlotinib, lapatinibgefitinib, erlotinib, lapatinib, the monoclonal antibody cetuximabcetuximab), imatinibimatinib, the monoclonal antibody trastuzumabtrastuzumab, and the Clostridium perfrigens enterotoxinClostridium perfrigens enterotoxin are currently under evaluation as molecularly targeted therapies for endometrial cancer.……
…….. Further investigationsFurther investigations addressed to better understand the signal transduction pathways that are disregulated in endometrial carcinogenesis could identify novel biological targets suitable for tailored therapies.