Transcript Prostate Cancer Symposium Bahamas

annual prostate cancer symposium
February 23, 2013 • 
The Kimmel Cancer Center, Philadelphia, PA
“Novel Therapeutic Strategies
for Prostate Cancer”
Lucia Languino
Dept of Cancer Biology
Thomas Jefferson University
What’s new in prostate cancer
research?
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Genetics
Prevention
Early detection
Diagnosis
Staging
Treatment
Surgery
Radiation treatment
Nutrition and lifestyle changes
Hormone treatment
Chemotherapy
Prostate cancer vaccines
Bone Pain
PROSTATE CANCER: DEVELOPING
A PERSONALIZED/PRECISION
MEDICINE APPROACH
Critical Issues in Prostate Cancer
• Risk and prevention
• Who needs to be treated-disease
stratification
• Understanding and treating resistance to
therapy
• Cardiovascular side effects of therapies
PROSTATE CANCER IS PREVENTABLE
THROUGH EARLIER SCREENING
AND DIAGNOSIS
Biomarkers
Despite significant progress in the investigation of
prostate cancer biomarkers, some men are
overdiagnosed with indolent CaP while others die
from aggressive disease diagnosed too late.
Developing markers to identify men with indolent
prostate cancer who will not be affected by disease
in their lifetimes and do not need treatment.
Developing markers to identify men with aggressive
disease who will benefit from local therapy and
those who are likely to fail local therapy and require
adjuvant intervention.
Biomarkers
Prognostic versus Diagnostic
Markers
Biomarkers: Bodily Fluids
Ongoing research:
A urine test for PCA3/PSA mRNA ratio is very specific for
prostate cancer and has been shown to have an excellent
negative predictive value in a population of men undergoing
biopsy.
Developing markers to minimize the number of unnecessary
prostate biopsies.
Bone Metastasis and Prostate Cancer
• 80% Prostate Cancer Patients have metastasis to bone.
• The mechanisms that promote metastasis and tumor
growth in the bone are poorly understood.
• Prostate cancer metastasis are mixed osteoblastic and
osteolytic; in contrast, to breast cancer bone
metastasis, which are osteolytic.
• In prostate cancer, targeting αv integrins by siRNA
markedly reduced PC3 xenografts in the bone (Bisanz
et al).
Cilengitide
• Cilengitide or EMD 121974 is cyclo(Arg-Gly-Asp-D-Phe-[NMe]Val)
developed by Merck [Dechantsreiter, J.Med.Chem, 1999]:
– It is N-methylated modification of 1st generation v3selective cyclic peptide cyclo(Arg-Gly-Asp-D-Phe-Val) or
cRGDfV.
– It’s 4 fold more active for v3 integrins than cRGDfV.
• Phase I safety data [Eskens, EJC, 2003]:
– based on 37 patients with solid tumor
– Well tolerated, no drug-related hematological toxicity
– No partial or complete responses with drug alone
• Cilengitide increases radiosensitivity of HUVECs and non-small cell
lung cancer cells in vitro. [Albert, IJROBP, 2006]
Cilengitide
• Merck Serono, a division of Merck KGaA, Darmstadt,
Germany, has enrolled in 2011 500 patients in the global
pivotal Phase III clinical study CENTRIC.
• CENTRIC was designed to assess the efficacy and safety of
Cilengitide in combination with standard treatment in 500
newly diagnosed glioblastoma patients. The primary endpoint
of the study is overall survival.
• Results of parallel novel pilot Prostate Cancer studies are
being evaluated at this time.
Cilengitide –
7 clinical trials
• NCI-6735: a phase II study for non-metastatic
castrate resistant prostate cancer, with PSA
progression despite hormonal therapy.
• NCI-6372: a phase II study for asymptomatic
castrate resistant metastatic prostate
cancer.
• NABTT-0306: a phase I/II multicenter study to
combine with RadioTherapy for Glioblastoma.
Integrins as Therapeutic Targets
• As with any drug target:
• High investment (time and
resources), high risk
• Current programs
• 25% antibodies
• 50% small molecules
• 25% other (anti-sense, RNAi, natural
products)