costi-mito_pisa_2014 - Mito

Proteomic based fingerprint
come biomarker predittivi e
farmacodinamici:
dall’idea al progetto AIDOC
Maria Paola Costi
UNIMORE
MITO-Pisa 4-5 Novembre 2014
Premesse e principi

I campioni di sangue possono contenere informazioni sullo
condizione del tumore e su biomarker farmacodinamici.

Un
singolo
biomarker
non
è
sufficientemente
affidabile/predittivo per descrivere una condizione del tumore.

Un biomarker profile ingegnierizzato e validato può fornire un
tool affidabile per valutare l’efficacia di un farmaco in campioni
clinici minimamente invasivi.
Protein based fingerprint
per caratterizzare l’efficacia di un farmaco in fase
pre-clinica su linee cellulari di tumore ovarico.
Uno studio di proteomic
fingerprint
basato
sulla
spettrometria di massa (MS)
permette l’identificazione di un
biomarker farmacodinamico di
efficacia del farmaco sulla base
della modulazione dei livelli
proteici indotti.
Biomolecules level change
in ovarian cancer cell lines
induced by peptdies
targeting thymidylate
synthase networks.
F.Genovese, MPCosti et al J Proteome Research, 2014
Studio traslazionale del proteomic fingerprint su campioni di EOC
da CT con pemetrexed in seconda linea (fase II).
Traslational study In collaboration with the Mayo Clinic of Berlin Charitè
(Prof.Jalid Sheouli,TOC-Eutroc)
Biopsies received end 2013
On 52 biopsies of clinical
from phase II clinical study
Biopsies were evaluated by pathologist and selected
Tissue biopsies with 70% cancer cell
were selected for proteomics approach
Panel di 25 proteine selezionate secondo i tre criteri.
Targeted Mass Spectrometry.
Heatmap of western blot data
in attesa dei dati di proteomica su 25 proteine
Dal lab scale al MISTO fingerprint
con
AIDOC
Proteine & Lipidi

Fingerprint mista di biomolecole MISTO fingerprint.

Trattazione statistica complessa multilivello che supera il
problema dell’uso di piattaforme MS diverse (Molecular
discovery company).

Veristrat-like technology*, implementata con lipidi,
biomolecule di natura diversa.

Impelmenta il TCGA (The Cancer Genome Atlas) in cui
biomolecole diverse vengono considerate in un unique
profile.
*VeriStrat, (commercially available by Biodesix, Boulder, CO, USA)
From clinic to omic readout through novel mass
spectrometry technologies:
development of biomolecules fingerprint (s) to predict
early response to antiangiogenetic drugs in ovarian
cancer patients.
AID-OC
The AID-OC project is based on the development of a
new diagnostic tool based on the MISTO fingerprint
MISTO fingerprint includes proteins, (and
autoantibodies) and lipids to be used as
pharmacodynamic (PD) markers in OC patients at the
earlier phase of the therapeutic protocol (a few weeks)
with the antiangiogenic drug becavcizumab associated
with chemotherapy.
To reach the objective AID-OC project will apply
proteomics and lipidomics studies on low invasive
samples (serum) based on the MITO16 clinical
trial in retrospective and then prospective studies.
The innovative tool includes Mass spectrometry
(MS), combined with an automatic integration of
the multiple omic data translated in an easy readout for friendly use by non-specialised personnel,
achieved using technologies from different
scientific fields.
Main objectives
Main goal is to help
physicians in the early
decision on the
continuation/change of
ovarian cancer (OC)
patient’s therapy
To overcome the
limitations of approaches
used so far to predict the
pharmacological
effectiveness of
bevacizumab using an
innovative technology
Partnership
PERT
MISTO
technology
design for
mass
spectrometr
y detection
Proteins&lipids &
autoantibodies
Identification/valid
ation in
retro/prospective
CT using MS
AID-OC
technology to
predict early the
response to
bevacizumab
with
chemotherapy in
ovarian cancer
patients
Interface
software , data
analyisis with
Easy read out
visualization
MISTO can
select patients
for
continuation of
the therapy.
Technology
handling for
non-specialised
personnel in
hospital daily
practice.
Workflow del progetto
Grazie per l’attenzione