1. NUOVI APPROCCI TERAPEUTICI NEL CARCINOMA PROSTATICO
Alfredo Berruti
Dipartimento di Scienze Cliniche e Biologiche
Università di Torino Azienda Ospedaliero Universitaria
San Luigi di Orbassano

2. N Engl J Med 2004;351:

3. Lancet 2010; 376: 1147–54

4. 4 4

5. CASTRATE RESISTANT PROSTATE CANCER
Gain-of-function in AR.
Mutations occurring
in the AR
ligand–binding domain
AR gene
amplification
Cross-talk with
growth factors
and growth factor
receptors
Changes in the
balance of
steroid receptor
coregulators
Availability of androgens in tumor microenvironment
Enzymatic conversion of other steroids to androgens in the local tumor environment, leading to an increase in the concentration and availability of androgens for the tumor.
Sharifi N et al. Clin Cancer Res 2009

6. Low AR
High AR 6

7. Low AR
High AR 7

8. AR MDV 3100 ABIRATERONE LHRH-A BICALUTAMIDE KETOCONAZOLO FLUTAMIDE
CIPROTERONE
LHRH-A
ABIRATERONE
KETOCONAZOLO AR
ANDROGENI

9. 9

10. 10

11. Chemotherapy pretreated patients!!!11

13. Mechanism of MDV3100 Lancet Oncol 2009; 10: 981–91
Yu Chen, Nicola J Clegg,
Howard I Scher
Lancet Oncol 2009;
10: 981–91

15. 15

16. 16

17. 17

18. only patients with asymptomatic disease were enrolled!!!

19. SIPULEUCEL-T TREATMENT FLOW

24. 24 24

25. 25 25

26. 26 26

27. 27 27

28. Trattamenti medici per il carcinoma prostatico “castrate resistant”
Ormonoterapia
Abiraterone
MDV3100
Vaccini
Sipoleucel ?
Farmaci a bersaglio
molecolare
Chemioterapia
Cabazitaxel
Inibitori del riassorbimento osseo
Ac Zoledronico
Denosumab

29. Sternberg C 2007 Disease Median Chemotherapy Burden survival indicated
Rising PSA only years? NO
Asymptomatic 18 to 24 months Case by case
Metastases
(limited)
Asymptomatic months YES
(extensive)
Symptomatic 9 to 18 months YES
PSA=prostate specific antigen
Sternberg C 2007

30. Quale strategie nel prossimo futuro?
Ormono terapia I linea LHRH-A
Ormono terapia II linea Abiraterone o MDV3100
Ormono terapia III linea Abiraterone o MDV3100
Paziente asintomatico
Paziente sintomatico
Vaccino
Chemioterapia

31. Quale strategie nel prossimo futuro?
Farmaci aventi
come bersaglio
il tumore
Farmaci aventi
come bersaglio
il microambiente

32. Bone marrow are a reservoir of cancer cells that eventually
metastasize elsewhere.
Clin Cancer Res 2008

34. ANTINEOPLASTIC AGENTS
BISPHOSPHONATES AS
ANTINEOPLASTIC AGENTS
may create an unfavorable microenvironment
for the survival and activity of cancer stem cell
in bone

36. Lancet 2011; 377: 813–22